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The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma

  • Ruigang Dou , Rongfeng Liu , Peng Su , Xiaohui Yu and Yanzhao Xu EMAIL logo
Published/Copyright: August 10, 2024
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Open Medicine
From the journal Open Medicine Volume 19 Issue 1

Abstract

Gap junction protein beta 3 (GJB3) has been reported as a tumor suppressor in most tumors. However, its role in lung adenocarcinoma (LUAD) remains unknown. The purpose of this study is to explore the role of GJB3 in the prognosis and tumor microenvironment of LUAD patients. The data used in this study were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and imvigor210 cohorts. We found that GJB3 expression was increased in LUAD patients and correlated with LUAD stages. LUAD patients with high GJB3 expression exhibited a worse prognosis. A total of 164 pathways were significantly activated in the GJB3 high group. GJB3 expression was positively associated with nine transcription factors and might be negatively regulated by hsa-miR-6511b-5p. Finally, we found that immune cell infiltration and immune checkpoint expression were different between the GJB3 high and GJB3 low groups. In summary. GJB3 demonstrated high expression levels in LUAD patients, and those with elevated GJB3 expression displayed unfavorable prognoses. Additionally, there was a correlation between GJB3 and immune cell infiltration, as well as immune checkpoint expression in LUAD patients

Keywords: lung adenocarcinoma; GJB3 ; transcription factors; hsa-miR-6511b-5p; immune; drug sensitivity

1 Introduction

Lung cancer is a life-threatening and aggressive type of cancer worldwide, and it is a primary cause of cancer-related mortality [1]. It is estimated that lung cancer occurred for approximately 11.4% of all new cancer cases and is responsible for 1.8 million deaths (18% of all cancer-associated mortalities) in 2020 [2]. Previous studies have reported that smoking is closely associated with the incidence of lung cancer [3,4]. Higher smoking intensity and duration could increase the risk and mortality of lung cancer, while a more extended time since smoking cessation can reverse this phenomenon [5], and former smokers who have recently quit smoking have a 50–80% reduction of lung cancer risk [6]. In addition, age, genetic factors, ethnicity, and race are also correlated with the incidence of lung cancer [7]. In recent years, the therapy and diagnosis of lung cancer have required some improvements, but the prognosis and outcome of lung cancer patients remain suboptimal [8].

According to histopathology, lung cancer is generally divided into two cell types, small cell lung cancer and non-small cell lung cancer (NSCLC). The NSCLC includes three histologic subtypes, squamous cell carcinoma, lung adenocarcinoma (LUAD), and large cell carcinoma, roughly accounting for 80–85% of lung cancer [9], and LUAD is the most common subtype of NSCLC [10]. LUAD is prone to metastasize at an early stage, and the average 5-year survival rate is less than 20% [11]. The therapeutic approaches for LUAD mainly include surgical resection, chemotherapy, radiotherapy, and immunotherapy [12]. Identifying patients with LUAD in the early stages is challenging due to metastasis occurring at the time of diagnosis [13]. Moreover, LUAD cells are able to rapidly acquire drug resistance after initial treatment and usually cannot be treated with chemotherapeutic agents [14,15]. Therefore, the 5-year overall survival rate of LUAD remains poor [8].

Gap junction protein beta 3 (GJB3) is a member of the connexin gene family, and it encodes the gap junction protein connexin 31(Cx31). It is reported that the mutation of GJB3 could cause erythrokeratoderma variabilis [16] and autosomal recessive/dominant non-syndromic hearing loss [17,18]. In addition, GJB3 has been reported as a tumor suppressor in the majority of tumors. In metastatic breast cancer of the bone, the patients with high GJB3 expression exhibit better prognosis [19], and the high GJB3 expression could reduce the migration, proliferation, and invasion ability of thyroid cancer cells [20]. However, the GJB3 is up-regulated in pancreatic ductal adenocarcinoma (PDAC) liver metastasis and GJB3 depletion could suppress the hepatic metastasis of PDAC cells [21]. However, the mechanism and function of GJB3 in tumorigenesis and the development of LUAD remain largely unknown. Thus, we systematically explored the potential effects of GJB3 in tumor microenvironment (TME), immunotherapy, and drug sensitivity of LUAD patients utilizing the bioinformatics methods.

2 Materials and methods

2.1 Subjects

The mRNA expression profiles of 585 samples with corresponding clinical information, including 526 LUAD and 59 normal samples, were acquired from The Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/tcga/) database. Among 585 samples, 502 samples contained complete survival information. The miRNA expression profile, copy number variation, and Mutation Annotation Format files were downloaded for subsequent analyses. Cell line expression profiles were downloaded from Cancer Cell Line Encyclopedia (CCLE, https://sites.broadinstitute.org/ccle).

The GSE36471 and GSE43458 datasets were collected from Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). GSE36471 included 117 LUAD samples (114 with complete survival information), and GSE43458 contained 80 LUAD and 30 normal samples.

Moreover, the 348 immunotherapy-experienced BLCA samples containing immunotherapy response status and survival information were obtained from the imvigor210 cohort.

2.2 Differential gene analysis

The differential gene analysis was performed between two groups utilizing the “limma” [22] function package in the R language (version 4.2.1, the same as below). The differentially expressed genes (DEGs) were screened by |Log2FC| > 1 and FDR < 0.05. The DEGs were then analyzed for Gene ontology (GO, comprising biological process [BP], molecular function [MF], and cellular component [CC]) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using the “clusterProfiler” function package (version 4.7.1.2) [23] in R language. Significantly enriched pathways were discovered at P < 0.05.

2.3 Gene set enrichment analysis (GSEA)

In the TCGA cohort, the patients were split into GJB3 high and GJB3 low groups according to the median GJB3 expression. The GSEA was performed using the R language function package “clusterprofiler” [23]. The significantly enriched pathways were screened by P < 0.05.

2.4 Survival analysis

The overall survival of different groups was estimated using the R language “survival” (https://cran.r-project.org/package=survival) and “survminer” packages (https://cran.r-project.org/package=survminer). The significance of differences in survival rates between different groups was tested using the log-rank. The multivariate Cox regression model was used to analyze whether the target gene could predict the survival of LUAD patients independently of other factors.

2.5 Nomogram prognostic model establishment

R language “rms” (https://CRAN.R-project.org/package=rms, version 6.6.0) package was used to establish a nomogram using independent prognostic factors identified by multivariate Cox regression analysis to predict 1-, 3-, and 5-year overall survival of patients. To assess the accuracy of the predictions, a calibration curve was plotted to observe the relationship between the predicted probability and the actual incidence. For each patient, three lines were drawn upward to determine the points received from the predictors in the nomogram. The sum of these points was located on the “Total points” axis. A line was drawn downward to assess the likelihood of 1-, 3-, and 5-year overall survival.

2.6 Immune cell infiltration

The CIBERSORT software [24] was applied to calculate the relative proportions of the 22 immune cells in the samples. CIBERSORT can describe the composition of immune infiltrating cells using the 547 preset barcode genes in the deconvolution algorithm based on the gene expression matrix. The immune score of samples was calculated using the “estimate” function package (https://R-Forge.R-project.org/projects/estimate/).

2.7 Screening of transcription factors correlated with the GJB3 expression

In TCGA-LUAD mRNA dataset, the highly expressed transcription factors were filtered based on the expression read counts median >1 and mean >10. The significantly differentially expressed transcription factors were selected using the DEGs between LUAD and normal samples according to Log2FC > 1 and FDR < 0.05. The correlation of transcription factors with GJB3 mRNA was calculated using Pearson correlation, and the transcription factors significantly correlated with GJB3 were screened according to P < 0.05 and Rho > 0.3.

2.8 Protein–protein interaction (PPI) network analysis

The STRING (https://string-db.org/, version 11.0) database [25] was employed to analyze the functional links between proteins. The Cytoscape (version 3.7.2) [26] was applied to visualize the PPI network.

2.9 Statistical analysis

Drug sensitivity was predicted using the “oncopredict” package [27] in the R language. The differences in gene expression and immune cell infiltration between groups were compared by the Wilcoxon rank sum test. Pearson correlation analysis was performed using the R language “cor” function. P < 0.05 were considered statistically significant.

3 Results

3.1 GJB3 was highly expressed in LUAD patients and correlated with LUAD stages

In the TCGA and GSE43458 cohorts, we found that the GJB3 was up-regulated in LUAD samples (LUAD vs normal, Figure 1a and b). In CCLE database, the GJB3 was also highly expressed in lung cancer cells (Figure 1c). Next, we analyzed GJB3 expression in different pathological stages and TNM stages of LUAD patients in the TCGA cohort. Compared to stage I, GJB3 expression was increased in stage II and stage III (Figure 1d). Moreover, GJB3 expression was differential between T1 and T2, T1 and T3, T2 and T3, N0 and N1, N0 and N2 (Figure 1e and f). However, there was no significant difference observed in the expression of GJB3 between stage I and stage IV, T1 and T4, N0 and N3, which might be attributed to the relatively small sample size of patients with tumor metastasis and advanced LUAD. Additionally, the expression of GJB3 displayed no significant difference between M0 and M1 (Figure 1g), indicating that the slightly decreased expression of GJB3 in advanced stage was not seemingly linked to lung cancer metastasis. Moreover, in the GSE36471 dataset, we analyzed the expression of GJB3 in different stages of LUAD patients, and obtained the same results as TCGA cohort (Figure S1).

Figure 1 GJB3 was highly expressed in LUAD patients. (a and b) The expression of GJB3 between LUAD samples and normal samples in TCGA and GSE43458 cohorts. (c) The expression of GJB3 between LUAD cells and normal cells in the CCLE cohort. (d) The expression of GJB3 in different pathological stages of LUAD (stage I–stage Ⅳ). (e–g) The expression of GJB3 in TNM classification of LUAD patients. The Wilcoxon rank-sum test was used to compare gene expression between two groups. A value of P < 0.05 was taken to indicate statistical significance.
Figure 1

GJB3 was highly expressed in LUAD patients. (a and b) The expression of GJB3 between LUAD samples and normal samples in TCGA and GSE43458 cohorts. (c) The expression of GJB3 between LUAD cells and normal cells in the CCLE cohort. (d) The expression of GJB3 in different pathological stages of LUAD (stage I–stage Ⅳ). (e–g) The expression of GJB3 in TNM classification of LUAD patients. The Wilcoxon rank-sum test was used to compare gene expression between two groups. A value of P < 0.05 was taken to indicate statistical significance.

3.2 LUAD patients with high GJB3 expression exhibited a worse prognosis

As shown in Figure 2a and b, the GJB3 high group was associated with a worse prognosis of LUAD patients compared to GJB3 low group in both TCGA and GSE36471 cohorts. The time-dependent receiver operating characteristic curve analysis showed that the area under the curve (AUC) for overall survival at 1, 2, 3, and 5 years was 0.601, 0.639, and 0.631, respectively (Figure 2c). In TCGA cohort, the multivariate Cox regression analysis including GJB3, gender, and stage showed that GJB3 could be an independent predictor of prognosis in LUAD patients (Figure 2d). Next, we constructed a nomogram model using GJB3, age, and stage (Figure 2e). The calibration curves of 1, 3, and 5 years were closer to the ideal curve (a 45° line passing through the origin of the coordinate axis with a slope of 1) in the calibration map, which indicated that the nomogram model predicted outcomes at 1, 3, and 5 years were consistent with the actual outcomes (Figure 2f–h).

Figure 2 Patients with high GJB3 expression exhibited worse prognosis in LUAD. (a and b) The KM survival curves of GJB3 high and GJB3 low groups in TCGA and GSE36471 cohorts. (c) The AUC for overall survival at 1-, 2-, 3-, and 5-year. (d) Forest plot of multivariate Cox regression analysis in TCGA cohort. (e) The nomogram model. (f–h) The calibration curves for predicting the probability of 1-, 3-, and 5-year overall survival in LUAD patients. The Wilcoxon rank-sum test was used to compare gene expression between two groups. A value of P < 0.05 was taken to indicate statistical significance.
Figure 2

Patients with high GJB3 expression exhibited worse prognosis in LUAD. (a and b) The KM survival curves of GJB3 high and GJB3 low groups in TCGA and GSE36471 cohorts. (c) The AUC for overall survival at 1-, 2-, 3-, and 5-year. (d) Forest plot of multivariate Cox regression analysis in TCGA cohort. (e) The nomogram model. (f–h) The calibration curves for predicting the probability of 1-, 3-, and 5-year overall survival in LUAD patients. The Wilcoxon rank-sum test was used to compare gene expression between two groups. A value of P < 0.05 was taken to indicate statistical significance.

3.3 Pathways correlated with GJB3 in LUAD

In the TCGA cohort, we identified 602 DEGs between GJB3 high and GJB3 low groups. Enrichment analysis showed that these DEGs were significantly enriched in 217 GO and 25 KEGG pathways (Table S1). The top 20 GO terms (including 10 BP, 2 CC, and 8 MF) and KEGG pathways are presented in Figure 3a and b, respectively. Moreover, GSEA showed that a total of 164 pathways were significantly activated in GJB3 high group compared to GJB3 low group (Table S2). Among these 164 pathways, multiple pathways, such as cytokine–cytokine receptor interaction, nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway, and natural killer cell-mediated cytotoxicity were correlated with the progression of tumors (Figure 3c–h).

Figure 3 Pathways correlated with GJB3 in LUAD. The top 20 significantly enriched GO (a) and KEGG pathways (b) of 602 DEGs. BP: biological process; CC: cellular component; MF: molecular function. (c) Cytokine–cytokine receptor interaction. (d) NLR signaling pathway. (e) Natural killer cell mediated cytotoxicity. (f) Cell cycle. (g) PI3K-Akt signaling pathway. (h) TNF signaling pathway.
Figure 3

Pathways correlated with GJB3 in LUAD. The top 20 significantly enriched GO (a) and KEGG pathways (b) of 602 DEGs. BP: biological process; CC: cellular component; MF: molecular function. (c) Cytokine–cytokine receptor interaction. (d) NLR signaling pathway. (e) Natural killer cell mediated cytotoxicity. (f) Cell cycle. (g) PI3K-Akt signaling pathway. (h) TNF signaling pathway.

3.4 Nine transcription factors were positively correlated with GJB3 in LUAD

We identified 55 transcription factors that were differentially expressed and more highly expressed in LUAD and calculated the correlation of 55 transcription factors with GJB3 expression. We found that the expressions of nine transcription factors were positively associated with GJB3 expression (Table 1, Figure 4a–i).

Table 1

Transcription factors associated with GJB3 expression in LUAD patients

Transcription factors Rho P-value
HMGA1 0.478233283 9.15 × 10−35
DNTTIP1 0.348650593 3.66 × 10−18
ZNF598 0.339133563 3.28 × 10−17
GTF2IRD1 0.331320183 1.87 × 10−16
NFE2L3 0.316108808 4.84 × 10−15
NME2 0.312032456 1.12 × 10−14
NR2F6 0.311606081 1.22 × 10−14
TCF3 0.306398541 3.51 × 10−14
MYBL2 0.304855148 4.78 × 10−14
Figure 4 Nine transcription factors were positively correlated with GJB3, and the expression of GJB3 was regulated by hsa-miR-6511b-5p in LUAD. (a–i) The correlation of nine transcription factors of GJB3. (j) The expression of hsa-miR-6511b-5p in GJB3 high and GJB3 low groups. (k) The correlation of hsa-miR-6511b-5p expression and GJB3 expression.
Figure 4

Nine transcription factors were positively correlated with GJB3, and the expression of GJB3 was regulated by hsa-miR-6511b-5p in LUAD. (a–i) The correlation of nine transcription factors of GJB3. (j) The expression of hsa-miR-6511b-5p in GJB3 high and GJB3 low groups. (k) The correlation of hsa-miR-6511b-5p expression and GJB3 expression.

3.5 GJB3 expression might be regulated by hsa-miR-6511b-5p in LUAD

We identified 35 targeted miRNAs of GJB3 (Table S3) utilizing the mirDIP database (http://ophid.utoronto.ca/mirDIP/). In TCGA-LUAD, we investigated the expression of 35 miRNA in GJB3 high and GJB3 low groups. The hsa-miR-6511b-5p expression was remarkably differential between GJB3 high and GJB3 low groups (Figure 4j) and exhibited a significantly negative correlation with GJB3 expression (Figure 4k). These results indicated that GJB3 expression might be regulated by hsa-miR-6511b-5p in LUAD.

3.6 GJB3 was correlated with the immune cell infiltration and immune checkpoint expression in LUAD

Subsequently, we found that the ESTIMATE Score and Immune Score levels were observably increased and Tumor Purity level was remarkably decreased in GJB3 high group than that in GJB3 low group (Figure 5a). In addition, we calculated the relative proportions of 22 immune cell infiltration (Figure 5b) and analyzed the level of immune cell infiltration in GJB3 high and GJB3 low groups, and found that the levels of Plasma.cells, T.cells.CD4.memory.resting, T.cells.gamma.delta, Macrophages.M0, Macrophages.M1, Macrophages.M2, Mast.cells.restin, and Neutrophils were observably differential between in GJB3 high and GJB3 low groups (Figure 5c). Figure 5d shows that the expression of PD-1 (PDCD1), CTLA-4, PD-L1 (CD274), PD-L2 (PDCD1LG2), CD80, CD86, LAG-3, and TIGIT were significantly increased in GJB3 high group than that in GJB3 low groups.

Figure 5 GJB3 was associated with the immune cell infiltration and immune checkpoint expression in LUAD. (a) The level of StromalScore, ImmuneScore, ESTIMATEScore, and TumorPurity in GJB3 high and GJB3 low groups. (b) The relative proportions of 22 immune cell infiltration. (c) The level of immune cell infiltration in GJB3 high and GJB3 low groups. (d) The expression of PD-1 (PDCD1), CTLA-4, PD-L1 (CD274), PD-L2 (PDCD1LG2), CD80, CD86, LAG-3, and TIGIT in GJB3 high and GJB3 low groups. PD-1 (PDCD1) was immune checkpoint marker of T cells, neutrophils, NK cells, NKT cells, monocytes, DCs, B cells. PD-L1 and PD-L2 were ligands for PD-1. CTLA-4 was immune checkpoint marker of T cells. CD80 and CD86 were ligands for CTLA-4. LAG-3 was immune checkpoint marker of T cells, NK cells, DC cells, and B cells. TIGIT was immune checkpoint marker of T cells, NK cells, monocytes, and neutrophils.
Figure 5

GJB3 was associated with the immune cell infiltration and immune checkpoint expression in LUAD. (a) The level of StromalScore, ImmuneScore, ESTIMATEScore, and TumorPurity in GJB3 high and GJB3 low groups. (b) The relative proportions of 22 immune cell infiltration. (c) The level of immune cell infiltration in GJB3 high and GJB3 low groups. (d) The expression of PD-1 (PDCD1), CTLA-4, PD-L1 (CD274), PD-L2 (PDCD1LG2), CD80, CD86, LAG-3, and TIGIT in GJB3 high and GJB3 low groups. PD-1 (PDCD1) was immune checkpoint marker of T cells, neutrophils, NK cells, NKT cells, monocytes, DCs, B cells. PD-L1 and PD-L2 were ligands for PD-1. CTLA-4 was immune checkpoint marker of T cells. CD80 and CD86 were ligands for CTLA-4. LAG-3 was immune checkpoint marker of T cells, NK cells, DC cells, and B cells. TIGIT was immune checkpoint marker of T cells, NK cells, monocytes, and neutrophils.

3.7 GJB3 was correlated with drug sensitivity in LUAD

Finally, we analyzed the correlation of GJB3 with drug sensitivity (IC50 values of drugs) using the R language “oncoPredict” package [27]. The results showed that GJB3 exhibited a significantly negative correlation with 86 drugs and a positive association with 53 drugs (Table S4). We selected the six drugs in which the absolute value of the correlation coefficient was greater than 0.3 (Figure 6a) and compared their IC50 between GJB3 high and GJB3 low groups. We found that the IC50 of negatively related drugs such as VX.11e_2096 was lower in GJB3 high group compared to GJB3 low group, while the positively related drugs were higher (Figure 6b). These results indicated that GJB3 could be a promising target of lung cancer therapy.

Figure 6 GJB3 was correlated with drug sensitivity in LUAD. (a) The correlation of six drugs with GJB3. (b) The IC50 of six drugs in GJB3 high and GJB3 low groups.
Figure 6

GJB3 was correlated with drug sensitivity in LUAD. (a) The correlation of six drugs with GJB3. (b) The IC50 of six drugs in GJB3 high and GJB3 low groups.

4 Discussion

LUAD is a markedly heterogeneous entity and it has the highest incidence among NSCLC and is characterized by various histologic subtypes, a high rate of metastasis, and recurrence [28,29]. Common symptoms of LUAD include dyspnea, chest pain, cough, and weight loss. Previous studies have indicated that aberrant expression of genes was also important mutagenic factors of LUAD [30]. For example, the level of NPM1 expression was remarkably increased in LUAD patients and was correlated with a prognosis of LUAD patients [31]. The expression of FGL2 was lower in LUAD, and the patients with high FGL2 expression displayed a better prognosis. Moreover, the high FGL2 expression was associated with the infiltration of immune cells in LUAD [32]. GJB3 was initially mapped to chromosome 1p35-p33, and its mutations participated in the non-syndromic hearing loss and two major conditions, erythrokeratodermia variabilis et progressive [16,17]. Moreover, several studies have suggested that GJB3 is a tumor suppressor in many cancers. However, the potential roles of GJB3 in LUAD were largely unknown. Thus, we explored the potential effects of GJB3 in TME, immunotherapy, and drug sensitivity in LUAD, and found that the GJB3 was highly expressed in LUAD patients, and the patients with high GJB3 expression exhibited poor prognosis. Moreover, GJB3 was associated with the immune cell infiltration, immune checkpoints expression, and drug sensitivity in LUAD.

First, we analyzed GJB3 expression in LUAD samples in different pathological stages and TNM classification of LUAD patients. We found that the GJB3 was up-regulated in LUAD patients, and GJB3 was correlated with pathological stages and TNM classification. Although previous research has shown that GJB3 expression was increased in PDAC liver metastasis [21], however, there was no significant difference observed in the expression of GJB3 between stage I and stage IV, T1 and T4, N0 and N3, M0 and M1, which might be attributed to the small sample size of advanced LUAD patients. In addition, the patients with high GJB3 expression exhibited a worse prognosis in LUAD. In PDAC liver metastatic mice, the GJB3 overexpression was correlated with poor prognosis, and GJB3 knockdown could alleviate the liver metastasis [21]. These pieces of evidence showed that GJB3 might be a cancer-promoting gene in LUAD. However, GJB3 expression was decreased in thyroid cancer samples, and GJB3 overexpression could reduce the proliferation, migration, and invasion of thyroid cancer cells [20]. In metastatic breast cancer of bone, the patients with high GJB3 expression exhibit better prognosis [19]. Accordingly, GJB3 might serve as a cancer-promoting gene in adenocarcinoma and as a tumor suppressor gene in certain cancers, such as thyroid cancer and breast cancer. We also found that GJB3 expression was positively correlated with nine transcription factors. Among these, HMGA1 [33], NME2 [34], NR2F6 [35], and MYBL2 [36] were found to be highly expressed in LUAD patients, and high expression of HMGA1 [37], NME2 [34], and MYBL2 [38] was correlated with inferior prognosis of LUAD patients. Accordingly, HMGA1, NME2, and MYBL2 act as oncogenic transcription factors in LUAD. It has been reported that silencing HMGA1 significantly reduced cell proliferation and glycolysis while promoting cell apoptosis in LUAD [33]. Overexpression of HMGA1 strongly stimulated LUAD cell growth and metastasis, while silencing HMGA1 inhibited LUAD cell growth and metastasis [39]. It was demonstrated that the overexpressing miR-26a in a LUAD cell line inhibited cell migration, invasion, and proliferation by targeting HMGA1 [40]. MYBL2 acts as a transcriptional activator in LUAD cells [41]. It might control cell cycle genes by binding to the promoters of highly expressed genes in LUAD cells and cooperating with FOXM1 [41]. Furthermore, MYBL2 was shown to interact with the LOXL1-AS1 promoter, and MYBL2 knockdown may counterbalance miR-423-5p repression-mediated increase in the progression of LOXL1-AS1 downregulated LUAD cells [42]. We also found that GJB3 might be regulated by hsa-miR-6511b-5p in LUAD. Some recent studies also suggested the regulator role of hsa-miR-6511b-5p in different cancers. In colorectal cancer, hsa-miR-6511b-5p could inhibit cancer cell migration and invasion through methylation of CD44 by targeting BRG1 [43]. In lymphoma, LncHOTAIR overexpression promoted the progression of cancer via regulating the hsa-miR-6511b-5p/ATG7 axis [44]. Moreover, high expressions of miR-6511b-5p at 6 h after the return of spontaneous circulation predicted poor outcomes in cardiac arrest patients [45]. Considering that GJB3 was highly expressed in LUAD and positively correlated with transcription factors HMGA1 and MYBL2, we hypothesized that hsa-miR-6511b-5p might impact the progression of LUAD via modulating the GJB3/HMGA1 or GJB3/MYBL2 pathways. Further investigation at cellular or clinical levels is required to validate this hypothesis.

The results of GO enrichment analysis revealed that DEGs between GJB3 high and GJB3 low groups were significantly enriched in the collagen-containing extracellular matrix (ECM). This ECM plays a critical role in the TME, with alterations in ECM being a key feature of the dysregulated microenvironment in lung cancer [46]. Collagens are the most abundant ECM proteins in the lung [47]. The abnormal production of collagen, posttranslational alterations affecting its stiffness, and the expression of collagen receptors provide a favorable microenvironment for the progression of lung cancer [46]. Studies have shown that high expression of collagen I in LUAD patients is associated with a shorter survival rate [48]. Therefore, it is suggested that GJB3 may have a significant impact on regulating BP related to collagens in LUAD. Additionally, GSEA showed that a total of 164 pathways were significantly activated in the GJB3 high group compared to the GJB3 low group, such as cytokine–cytokine receptor interaction, NLR signaling pathway, natural killer cell mediated cytotoxicity, PI3K-AKT signaling pathway, and TNF signaling pathway. Cytokines are important regulators and mobilizers. They could regulate the growth, proliferation differentiation, activation, and homeostasis of immune cells by binding to the corresponding receptors of cytokines [49,50]. In cancer, the cytokine receptor expression is increased, which can promote the immune evasion of tumor cells [51]. Cytokine–cytokine receptor interaction is a way in which cytokines respond to activation signals induced, and it has been demonstrated to play a critical role in tumors, especially in glioblastoma [49,52,53]. In addition, Zheng et al. have found that the hot LUAD tumors were significantly enriched in cytokine–cytokine receptor interaction [54]. NLRs play a major role in the interface between innate immunity and cancer in humans. NLR signaling pathway is also involved in the autophagy and apoptosis of inflammation-associated cancer [55]. The NLRs are categorized into five subfamily members: NLRA (CIITA), NLRB (NAIP), NLRC (NOD1, NOD2), NLRP (NLRP3), and NLRX (NLRX1) [56]. NAIP could inhibit the apoptosis induced by varieties of signals via the inactivation of CASP3, CASP7, and CASP9 [57]. NLRP3 abnormal activation was associated with inflammatory diseases. In LUAD, NLRP3 inflammasome activation could promote nicotine-induced cell proliferation and migration [58]. The NOD1 expression in T cells could impede the colitis-associated intestinal tumorigenesis through mediating the IFN-γ signaling [59], and NOD2 could suppress the tumorigenesis of colitis-associated cancer by downregulating NF-κB and MAPK pathways with the induction of IRF4 [60]. Wang et al. have suggested that the descended NOD2 expression was correlated with poor prognosis of LUAD, and the reduction of NOD2 expression in macrophages promotes the conversion of the M1 macrophages to M2 macrophages in LUAD [61]. These suggested that the different members of the NLRs signaling pathway play different functions in LUAD, implying that NLRs signaling pathway was activated in LUAD patients with high GJB3 expression was reasonable. Moreover, natural killer cell mediated cytotoxicity and PI3K-AKT signaling pathway were also associated with inflammatory process immune of tumors [62–64]. Collectively, these findings showed that the GJB3 might be involved in the immune microenvironment of LUAD by regulating multiple inflammation and immune-related pathways.

We also found that the levels of Plasma.cells, T.cells.CD4.memory.resting, T.cells.gamma.delta, Macrophages.M0, Macrophages.M1, Macrophages.M2, Mast.cells.restin, and Neutrophils were observably differential between in GJB3 high and GJB3 low groups. T cells were divided into CD4+T cells and the CD8+T cells [65]. CD4+T cells are auxiliary T cells, while CD8+T cells are cytotoxic T lymphocytes. CD4+T cells included several subsets, such as T helper 1 (Th1), Th2, Th9, and regulatory T cells (Tregs), CD4+T cells could indirectly involve in clearing infection via regulating the activity of macrophages, neutrophils, B cells, and other immune cells [66]. Tumor-associated macrophage infiltration plays critical roles in tumorigenesis and metastasis. Normally, macrophages contain two phenotypes (M1 macrophages and M2 macrophages). M1 macrophages are induced via the activation of lipopolysaccharide and could express pro-inflammatory cytokines. M2 macrophages are induced through IL-4 expression and could express anti-inflammatory cytokines. M1 macrophages could promote cancer cell elimination to restrain tumor progression, and M2 macrophages can induce an immunosuppressive effect to promote tumor progression [67]. The polarization of these two macrophages is a highly dynamic process. It has been found that about 85% of the macrophages in the tumor stroma are the M2 macrophages in the NSCLC patients with an average of 1-year survival [68]. M1 and M2 macrophages were significantly elevated in the NSCLC tissue than in the normal lung tissue [69]. Wang et al. discovered that the proportion of M1 macrophages was significantly higher in LUAD compared to normal tissues. Furthermore, they found that the high level of M1 macrophages was correlated with a poorer prognosis in patients with LUAD [70]. However, Jackute et al. have demonstrated that a higher level of infiltrating M2 macrophages was also correlated with inferior NSCLC prognosis [69]. In this study, we found that the high infiltration of M1 and M2 macrophages was associated with a poor prognosis of LUAD patients with high GJB3 expression. One probable explanation might be that tumor cells release monocyte chemotactic protein-2, which can recruit circulating M1 macrophages to the tumor location [71,72]. Moreover, abnormal gene expression also could increase the infiltration of M1-type macrophage in tumor [73]. Noteworthily, previous research has been divided on the relevance of M1 macrophages in NSCLC patient survival. Welsh and colleagues have found that the density of macrophage had positive correlation with survival of patient in the tumor islets [74]. Chen et al. have discovered that high density of tumor-infiltrating macrophages may increase NSCLC angiogenesis and cause adverse outcome [75]. Dai et al. have demonstrated that macrophages in the NSCLC islets were positively associated with survival, whereas in the tumor stroma macrophages were negatively associated with survival [68]. However, some studies showed that there was no association between the macrophage number and prognosis of NSCLC patients [76,77]. The immune cell infiltration results we observed might be the product of complex interactions among all members in TME, while deepening details should be further mined in the future.

The GJB3 might involve in the immune cell infiltration in LUAD. In addition, immune checkpoints, as negative regulators in the immune system, participated in the prevention of autoimmunity and protected tissues from immune damage [78]. Recently, the immunotherapy targeting immune checkpoint blockers, such as CTLA-4, PD-1, and PD-L1, changed the landscape of LUAD treatments [79]. The expressions of PD-1 (PDCD1), CTLA-4, PD-L1 (CD274), PD-L2 (PDCD1LG2), CD80, CD86, LAG-3, and TIGIT were significantly increased in GJB3 high group than that in GJB3 low group. These results suggested that GJB3 expression was closely correlated with immunotherapy in LUAD. Finally, we found that the GJB3 exhibited a significantly negative correlation with 86 drugs and a positive association with 53 drugs. LUAD cells are able to rapidly acquire drug resistance after initial treatment and usually cannot be treated with chemotherapeutic agents [14,15]. Xu et al. have indicated that GJB3 expression was decreased in papillary thyroid cancer, and the ginsenoside could increase GJB3 expression, thereby suppressing the proliferation and migration of thyroid cancer cells [20]. These studies suggested that the GJB3 might be a drug resistance related gene in LUAD, which warrants further exploration in future studies.

Although our study had presented the role of GJB3 in the prognosis and immune microenvironment of LUAD patients, it is important to acknowledge some limitations. First, we did not explore the mechanism by which GJB3 regulates immune cell infiltration in LUAD. Second, further investigation and exploration of the role of GJB3 in the prognosis of LUAD patients should be conducted through experimental clinical trials.

5 Conclusion

In summary, we found that the GJB3 was highly expressed in LUAD patients, and the patients with high GJB3 expression exhibited poor prognoses. Moreover, the GJB3 was associated with immune cell infiltration, immune checkpoint expression, and drug sensitivity in LUAD. Our findings might provide valuable information for further exploring the pathogenesis mechanism of LUAD and indicate that GJB3 might serve as a promising molecular target for the diagnosis and treatment of LUAD.

Abbreviations

AUC

area under the curve

CCLE

Cancer Cell Line Encyclopedia

CNV

copy number variation

Cx31

Connexin 31

DEGs

differentially expressed genes

ECM

extracellular matrix

GJB3

gap junction protein beta 3

GSEA

gene set enrichment analysis

LUAD

lung adenocarcinoma

NOD

nucleotide-binding oligomerization domain

NSCLC

non-small cell lung cancer

PDAC

pancreatic ductal adenocarcinoma

PPI

protein–protein interaction

SCLC

small cell lung cancer

TCGA

The Cancer Genome Atlas

Th1

T helper 1

TME

tumor microenvironment

Tregs

regulatory T cells

tel: +86 15833918856

Acknowledgements

Not applicable.

  1. Funding information: Not applicable.

  2. Author contributions: Conceptualization: Ruigang Dou; methodology, writing – original draft: Ruigang Dou and Rongfeng Liu; software, formal analysis: Rongfeng Liu, Peng Su, and Xiaohui Yu; data curation: Peng Su and Xiaohui Yu. writing – review & editing, project administration: Ruigang Dou and Yanzhao Xu; visualization: Rongfeng Liu and Yanzhao Xu; supervision: Ruigang Dou and Peng Su. All authors read and approved the final version to be published.

  3. Conflict of interest: The authors declare that they have no competing interests.

  4. Data availability statement: The data that support the findings of this study are available in the Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/tcga/) database, Cancer Cell Line Encyclopedia (CCLE, https://sites.broadinstitute.org/ccle), Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/), and STRING (https://string-db.org/,version 11.0) database.

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Received: 2023-06-30
Revised: 2024-03-26
Accepted: 2024-05-01
Published Online: 2024-08-10

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
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  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
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  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
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  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
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  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
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  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
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  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
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  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
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  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
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  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
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  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
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https://doi.org/10.1515/med-2024-0974
Keywords for this article
lung adenocarcinoma; GJB3; transcription factors; hsa-miR-6511b-5p; immune; drug sensitivity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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