Startseite Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
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Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients

  • Lixian Chang , Xuelian Cheng , Xingjie Gao , Yao Zou , Weiping Yuan , Li Zhang EMAIL logo und Xiaofan Zhu EMAIL logo
Veröffentlicht/Copyright: 9. November 2023
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Open Medicine
Aus der Zeitschrift Open Medicine Band 18 Heft 1

Abstract

Considering the connection between the Fanconi anemia (FA) signaling pathway and tumor development, we aim to investigate the links between the FA gene expression and the survival prognosis of acute myeloid leukemia (AML) patients. Our study begins by identifying two distinct clusters of pediatric AML patients. Following the batch matching of the TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts, the samples were divided into a training set and an internal validation set. A Lasso regression modeling analysis was performed to identify five signatures: BRIP1, FANCC, FANCL, MAD2L2, and RFWD3. The AML samples were stratified into high- and low-risk groups by evaluating the risk scores. The AML high-risk patients showed a poorer overall survival prognosis. To predict the survival rates, we developed an FA Nomogram incorporating risk score, gender, age, and French–American–British classification. We further utilized the BEAT-AML cohort for the external validation of FA-associated prognostic models and observed good clinical validity. Additionally, we found a correlation between DNA repair, cell cycle, and peroxide-related metabolic events and FA-related high/low risk or cluster 1/2. In summary, our novel FA-associated prognostic models promise to enhance the prediction of pediatric AML prognosis.

Keywords: Fanconi anemia; acute myeloid leukemia; prognosis; children; expression

1 Introduction

During myeloid differentiation, hematopoietic progenitor cells get blocked, resulting in acute myeloid leukemia (AML) [1,2,3]. AML is characterized by its high heterogeneity, associated with several factors, including cytogenetic abnormalities, genetic mutations, and changes in gene expression [1,2,3]. Pediatric AML constitutes approximately 15–20% of all cases of childhood leukemia [4,5]. Advancements in hematopoietic stem cell transplantation, molecular targeted therapy, immunotherapy, and genomic technology have improved prognosis and overall survival (OS) rates for pediatric AML. However, the mortality rate remains high [4,5]. Pediatric AML exhibits distinct genetic characteristics compared to adult AML [6]. Evaluating prognostic risk factors in AML is crucial for the management strategies or therapeutic advances in AML patients [1,2,3]. Several models have been reported for predicting the prognosis of AML patients, focusing on specific biological events [7,8,9]. For instance, a survival model based on 85 genes was reported to assess the AML prognosis [7]. Another study identified a 29-gene signature that could be a helpful predictor for therapy resistance in intensively treated adult AML patients [9]. However, fewer specific gene expression-based models or clusters were reported for predicting the prognosis of pediatric AML.

Fanconi anemia (FA) is characterized by autosomal or X-linked-recessive and autosomal-dominant genetic inheritance [10,11,12,13,14]. The pathogenesis of FA is associated with the FA signaling pathway, which contributes to genomic stability [10,11,12,13,14]. So far, 23 FA-related genes have been identified, such as FANCA/B/C and FANCD2 [10,11,12,13,14,15]. Extensive research has established strong connections between the FA signaling pathway and cancers [16,17,18,19]. FA patients are more susceptible to AML and other solid tumors [16,17,18,19,20,21]. For example, the FA pathway has shown potential as a treatment target for colorectal cancer [16]. Therefore, developing effective and reliable prognostic risk score models for AML is crucial by considering the expression pattern of FA signaling pathway genes.

Herein, we carried out a cluster analysis of pediatric AML cases based on the FA signaling pathway. We then identified five FA hub genes (including BRIP1, FANCC, FANCL, MAD2L2, and RFWD3). These genes were used to establish a novel FA-related prognostic model for pediatric AML patients.

2 Methods

2.1 Gene expression and clinical information

Gene expression matrix of the TPM (transcripts per million) type and a set of clinical traits were obtained from The Cancer Genome Atlas (TCGA)-LAML cohort using the “TCGAbiolinks” R package. We analyzed the expression pattern of each FA gene by combining datasets within a genotype-tissue expression (GTEx) and TCGA-LAML cohort. The data of TARGET-AML were obtained from the official website (https://ocg.cancer.gov/). We performed a statistical analysis using the wilcox.test or kruskal.test. The “GEOquery” R package was utilized to obtain the datasets of the GSE71014, GSE37642, and GSE12417 cohorts within the gene expression omnibus (GEO) database. Then, the expression matrix of TARGET-AML (n = 257), TCGA-LAML (n = 137), GSE71014 (n = 104), GSE37642 (n = 136), and GSE12417 (n = 78) was processed using the R language, and the batch correction was performed using the “sva” package. We then used the prcomp() function for the principal component analysis (PCA). The BEAT-AML cohort (n = 399) [22,23,24,25,26] was utilized as an external validation set.

2.2 Tumor clustering

We used the “ConsensusClusterPlus” R package [27] to cluster TARGET-AML samples according to the expression characteristics of FA signatures. Then, PCA was conducted. Additionally, we utilized the “survival” R package to perform the cluster-related prognostic analysis.

2.3 Lasso regression modeling construction

We performed Lasso regression modeling analysis using the datasets of TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts. The cases were divided into a training set (75%) and an internal validation set (25%). We used the “glmnet” R package to conduct a Lasso regression modeling analysis of the training set. The resulting model provided gene coefficients and risk score values. Risk scores were grouped according to their median values to determine high- and low-risk groups. The OS risk values for the internal validation set were also obtained. We plotted the risk profile, survival curves, and the survival status map. The hub gene expression profile was visualized as a heat map. Furthermore, we used the BEAT-AML cohort to externally validate the above FA-associated prognostic model.

2.4 Gene enrichment

Differentially expressed genes in two tumor clusters or risk groups were identified using a “limma” R package with a false discovery rate of 0.05 and a log2 fold change (log2FC) of 1. A “ggplot2” R package was used to generate an MA plot. Also, a heat map of FA genes and the clinical traits of age, gender, French–American–British (FAB), and clustering status were created. Gene enrichment analysis was performed, and the results were visualized using the “GOplot” R package [28]. Furthermore, gene set enrichment analysis (GSEA) was conducted by a “clusterProfiler” R package [29,30], and the results were visualized using the “gseaplot()” function of the enrichplot R package. Common members of differential genes between the risk and clustering groups were obtained, and the related gene ontology (GO)-Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed.

2.5 Cox regression

To assess the OS prognosis, the univariate/multivariate Cox regression analyses were conducted using a “survival” R package, considering the factors of prognostic risk score, FAB, gender, and age. Additionally, we performed external validation of the BEAT-AML cohort based on the multivariate Cox regression model associated with FA, using the predict() function. The forest plots were generated using the plot() R function. To evaluate the receiver operating characteristic (ROC) results for different survival times, we utilized the “survivalROC” R package and provided the value of area under the curve (AUC).

2.6 Nomogram prediction model

A cph () modeling analysis was performed using the “regplot” R package, and a Nomogram was obtained. The calibration curves of AML cases were plotted using the calibrate() function of the “ggstatsplot” R package. The C index value was obtained using the “rms” R package. In addition, the external validation dataset (BEAT-AML) was used to perform calibration curve analysis based on the FA Nomogram. The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were conducted using the “survIDINRI” R package. Finally, the decision curve analysis (DCA) was performed using the “stdca.R” package from www.decisioncurveanalysis.org.

3 Results

3.1 Analytic strategy

The schematic diagram of our analytic strategy is presented in Figure 1. We initially analyzed the expression profile of 23 FA genes and the clinical traits. Next, using these FA signatures, we identified two tumor subtypes (cluster 1/2) in AML samples by utilizing the clustering function of the “ConsensusClusterPlus” R package. Additionally, we extracted and performed batch correction on the expression matrix of TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts. This was done with FA-related genes, the FA expression matrix, and corresponding clinical traits. An internal validation and training set were randomly selected from the samples. The training set-based Lasso regression modeling analysis was then conducted. We conducted multivariate Cox regression analyses. Nomograms and related calibrate curves were plotted as well. We assessed the clinical effectiveness of FA models by DCA. Additionally, survival, differential, and enrichment analyses of GO, KEGG, and GSEA were performed after risk or cluster grouping. FA-related models were validated in both the internal and external validation cohorts.

Figure 1 A schematic diagram of the study design.
Figure 1

A schematic diagram of the study design.

3.2 Expression profile

We analyzed the expression features of FA genes based on the combined datasets from the GTEx and TCGA-LAML cohorts.

As shown in Figure S1, we observed increased expression levels in the tumor group for FANCA, BRCA2, FANCG, FANCM, SLX4, ERCC4, and FAAP100 (all p < 0.05), while a decreased level was observed for FANCB, FANCC, FANCD2, FANCE, FANCI, FANCL, RAD51C, RAD51, BRCA1, UBE2T, XRCC2, MAD2L2, and RFWD3 (all p < 0.05) compared with the normal group. Additionally, there were expression differences for all FA genes, except FANCG, among different FAB types (Figure 2, all p < 0.05). We found a slightly higher expression of RAD51 (Figure S2, p < 0.05) and UBE2T (p < 0.05) in the male group. Furthermore, as shown in Figure S3, we observed positive correlations between the age factor and expression levels of FANCC and FANCE (p < 0.001).

Figure 2 Correlation between FA gene expression and FAB. Box plots display each FA gene’s expression difference among different FAB types for the TARGET-AML cohort. A kruskal.test() was performed. *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 2

Correlation between FA gene expression and FAB. Box plots display each FA gene’s expression difference among different FAB types for the TARGET-AML cohort. A kruskal.test() was performed. *p < 0.05, **p < 0.01, ***p < 0.001.

3.3 Tumor clustering analysis

Next, we conducted a tumor clustering analysis based on the expression profile of FA genes within TCGA-LAML (Figure 3a) and TARGET-AML (Figure 3b) datasets. We separated these AML clusters using a PCA approach for both cohorts. However, we found a statistical difference in OS survival between the two clusters only for the TARGET-AML (Figure 3b, p = 1.153 × 10−3) but not for the TCGA-LAML (Figure 3a). Specifically, the pediatric AML patients of TARGET in cluster 2 showed a worse OS prognosis compared to those in cluster 1 (Figure 3b). We provided heat map data in Figure 3c, showing the association between FA gene expression and clinical information. Furthermore, a significant difference was observed in all FA gene expressions between clusters 1 and 2 (Figure S4, all p < 0.05).

Figure 3 Tumor clustering analysis of FA genes. (a) AML patients from the TCGA-LAML were clustered according to the expression characteristics of FA-related genes. A PCA was performed to evaluate the classification effect on tumor clusters. The FA-specific prognostic curve of OS is also provided. (b) Similar analyses were conducted for the TARGET-AML cohort. (c) The correlation between FA gene expression and various clinical traits, including age, gender, FAB, and clusters, was analyzed. A heat map is provided. (d and e) The differential gene identification of the two clusters was completed, and a volcano plot is provided (d). The GO/KEGG (e) and GSEA (f) gene enrichment analyses were then conducted.
Figure 3

Tumor clustering analysis of FA genes. (a) AML patients from the TCGA-LAML were clustered according to the expression characteristics of FA-related genes. A PCA was performed to evaluate the classification effect on tumor clusters. The FA-specific prognostic curve of OS is also provided. (b) Similar analyses were conducted for the TARGET-AML cohort. (c) The correlation between FA gene expression and various clinical traits, including age, gender, FAB, and clusters, was analyzed. A heat map is provided. (d and e) The differential gene identification of the two clusters was completed, and a volcano plot is provided (d). The GO/KEGG (e) and GSEA (f) gene enrichment analyses were then conducted.

The differential genes of the two clusters were obtained, and a volcano plot is shown in Figure 3d. The GO/KEGG enrichment analysis data (Figure 3e) revealed that these genes were associated with the events related to the “cell cycle,” “DNA replication,” and peroxide-related events such as “hydrogen peroxide metabolic process,” and “peroxidase activity.” The GSEA result further showed a series of genes linked to DNA repair events, such as “nucleotide excision repair” and “homology-directed repair,” as well as cell cycle events, such as “M_phase” and “cell cycle checkpoints” (Figure 3f). These findings suggest a connection between the pediatric AML FA subtypes and DNA repair, cell cycle, and peroxide-related metabolic events.

3.4 Lasso regression model

We initially conducted batch matching on the TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts (Figure 4a). Subsequently, we used 75% of the samples as a training set. Using the expression feature of FA genes, we performed a Lasso regression modeling analysis (Figure 4b). Our model identified five hub genes with correlation coefficients: BRIP1 (0.284), FANCC (−0.031), FANCL (0.022), MAD2L2 (0.270), and RFWD3 (−0.068). The results, including the expression/risk profile, survival curve, and survival status of the training and internal validation sets, are presented in Figure 4c–d. We observed an increased mortality status in AML cases as the risk value increased. Furthermore, the high-risk group exhibited a worse OS prognosis than the low-risk group (Figure 4c, p = 7.358 × 10−5; Figure 4d, p = 7.249 × 10−3).

Figure 4 Lasso regression modeling analysis of FA. (a) We performed the Lasso regression modeling analysis based on the expression matrix of FA-related genes in TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts. A PCA plot shows the batch correction of the expression matrix. (b) Based on the training set, the Lasso regression modeling analysis was performed. (c and d) The data of the hub gene expression profile, risk profile, survival status map, and survival curve are provided in the training set (c) and internal validation set (d).
Figure 4

Lasso regression modeling analysis of FA. (a) We performed the Lasso regression modeling analysis based on the expression matrix of FA-related genes in TARGET-AML, TCGA-LAML GSE71014, GSE12417, and GSE37642 cohorts. A PCA plot shows the batch correction of the expression matrix. (b) Based on the training set, the Lasso regression modeling analysis was performed. (c and d) The data of the hub gene expression profile, risk profile, survival status map, and survival curve are provided in the training set (c) and internal validation set (d).

3.5 Prognostic analysis

In the Cox regression analyses of TCGA-LAML, the age factor was found to be correlated with worse clinical OS prognosis in adult AML patients (Figure 5a, HR > 1, p < 0.001). For the pediatric AML cases in the TARGET-AML cohort, we observed a relationship between higher risk scores and worse clinical OS prognosis (Figure 5b, all HR > 10, p < 0.001). The relationship between hub gene expression and clinical traits was visualized as a heatmap in Figure 5c. Furthermore, we performed ROC analysis to assess the OS predictive value of our model. Figure 5d shows that the AUC values were greater than 0.62 for 1-, 3-, 5-year survival time. These suggested that our FA model exhibits good predictive value for OS in pediatric AML patients.

Figure 5 Prognostic analyses of TCGA-LAML and TARGET-AML. Targeting the factors (prognostic risk score, FAB, gender, and age), we performed the univariate/multivariate Cox regression analyses to evaluate the prognosis of OS for the TCGA-LAML (a) and TARGET-AML (b). We created a heatmap that combines the expression of hub genes with related clinical traits (c). Based on the risk score, we conducted the ROC analyses to assess the OS prognosis of TARGET-AML for different survival time points (d).
Figure 5

Prognostic analyses of TCGA-LAML and TARGET-AML. Targeting the factors (prognostic risk score, FAB, gender, and age), we performed the univariate/multivariate Cox regression analyses to evaluate the prognosis of OS for the TCGA-LAML (a) and TARGET-AML (b). We created a heatmap that combines the expression of hub genes with related clinical traits (c). Based on the risk score, we conducted the ROC analyses to assess the OS prognosis of TARGET-AML for different survival time points (d).

3.6 Nomogram

We conducted the Nomogram and related assessments. Among the hub genes, there were higher expression levels of BRIP1 (Figure 6a, p < 0.001), FANCL (p < 0.05), and MAD2L2 (p < 0.001) in the high-risk group, compared with the low-risk group. By combining the risk score, gender, age, and FAB, we established a Nomogram to predict the OS rates of a pediatric AML case. The Nomogram, shown in Figure 6b, predicted the 1-, 3-, and 5-year survival rates at 0.34, 0.292, and 0.0881, respectively. The calibration plot curve in Figure 6c showed a high overlap between the predicted and observed value lines. The C index value of 0.66 was obtained (Figure 6c). Furthermore, NRI and IDI results suggested that the predictive function of the model improved after incorporating the risk score factor (Figure 6d, all IDI > 0, NRI > 0, p < 0.05). The DCA results (Figure 6e) further showed a better clinical validity of the “age + gender + FAB + risk score” group than other groups.

Figure 6 Nomogram and related assessment analyses. (a) The expression difference of FA hub genes between high- and low-risk groups is presented. (b) A Nomogram is constructed to forecast the 1-, 3-, and 5-year survival rates of a given AML case. Furthermore, the outcomes of the calibration plot curve (c), NRI/IDI assessment (d), and DCA (e) are provided.
Figure 6

Nomogram and related assessment analyses. (a) The expression difference of FA hub genes between high- and low-risk groups is presented. (b) A Nomogram is constructed to forecast the 1-, 3-, and 5-year survival rates of a given AML case. Furthermore, the outcomes of the calibration plot curve (c), NRI/IDI assessment (d), and DCA (e) are provided.

3.7 External validation analysis

Based on the FA-associated prognostic models mentioned above, we conducted external validation using the BEAT-AML cohort. As shown in Figure 7a, it can be observed that AML cases with a high FA-associated risk score showed a poorer prognosis (p = 3.612 × 10−2). Furthermore, an external validation of the multivariate Cox regression model associated with FA was conducted, revealing a favorable predictive value for AML patients, particularly for the 1-year survival time (AUC = 0.71), as depicted in Figure 7b. A calibration plot curve was also generated using the external validation set, illustrating a substantial concurrence between the predicted and observed value lines (Figure 7c). These results serve to substantiate the good predictive capability of our FA-associated prognostic models.

Figure 7 External validation of FA-associated prognostic models. (a) Based on the Lasso regression modeling of FA genes, we performed the survival curve analysis using the external validation cohorts (BEAT-AML). (b) The ROC results of the external validation set for 1-, 2-, and 3-year survival times were obtained based on the FA-associated multivariate Cox regression model. (c) Based on the FA Nomogram, we also performed the calibration curve analysis of the external validation set.
Figure 7

External validation of FA-associated prognostic models. (a) Based on the Lasso regression modeling of FA genes, we performed the survival curve analysis using the external validation cohorts (BEAT-AML). (b) The ROC results of the external validation set for 1-, 2-, and 3-year survival times were obtained based on the FA-associated multivariate Cox regression model. (c) Based on the FA Nomogram, we also performed the calibration curve analysis of the external validation set.

3.8 Prognostic risk-related differential gene analysis

We identified a series of differential genes (n = 65) based on the high- and low-risk grouping. The results were visualized via an MA plot (Figure 8a) and a heat map (Figure 8b). Further analysis of these differential genes was conducted using GO and KEGG enrichment approaches (Figure 8c). Our findings revealed the biological metabolic processes, such as the “antibiotic metabolic process” and “cellular oxidant detoxification.” Additionally, GSEA results showed the enrichment of events, including “DNA repair,” “G2M checkpoint,” and “oxidative phosphorylation” (Figure 8d). We also obtained 24 common members of differential genes between the risk and clustering groups (Figure 8e) and performed the gene enrichment analyses of GO-KEGG (Figure 8f). This analysis highlighted peroxide-related events, including the “hydrogen peroxide catabolic process” and “peroxidase activity.”

Figure 8 Prognostic risk-related differential gene analysis. (a and b) The differential gene identification between the high- and low-risk groups was performed, and the MA plot (a) and heat map (b) are provided to visualize the data. Gene enrichment analyses of GO-KEGG (c) and GSEA (d) were conducted to gain further insights. (e and f) Common members of differential genes between the risk and clustering groups were obtained, and gene enrichment analyses of GO-KEGG were performed to explore the functional significance.
Figure 8

Prognostic risk-related differential gene analysis. (a and b) The differential gene identification between the high- and low-risk groups was performed, and the MA plot (a) and heat map (b) are provided to visualize the data. Gene enrichment analyses of GO-KEGG (c) and GSEA (d) were conducted to gain further insights. (e and f) Common members of differential genes between the risk and clustering groups were obtained, and gene enrichment analyses of GO-KEGG were performed to explore the functional significance.

4 Discussion

We developed a prospective predictive model for AML by focusing on the FA signaling pathway. The consensus clustering of AML patients from the TCGA-LAML and TARGET-AML datasets was conducted using bioinformatics strategies. We identified two distinct clusters based on the expression patterns of FA signatures. Interestingly, we found a positive correlation between tumor clustering and OS prognosis only in pediatric AML cases but not in adult AML. Our novel FA-based tumor clustering approach may be helpful for the diagnosis and therapy of pediatric AML.

The close correlation between AML and mutations has led to the primary focus on correlation analysis of gene mutations in AML patients. This analysis aims to guide clinical treatment and evaluate prognosis [1,2,3,7,8,9,31]. For instance, in a previous study, we conducted a stratified prognostic analysis of different clinical subgroups in 132 children with AML-based data on gene mutations and related clinical traits [31]. Herein, we explore the potential correlation between FA-related models and the prognosis of AML patients, explicitly focusing on expression features of FA pathway genes. We developed a novel FA model for AML using the Lasso approach. Our multivariate Cox regression analysis also showed that a higher risk score is linked to a worse clinical OS prognosis, specifically in the TARGET-AML cohort rather than the TCGA-LAML cohort. These findings suggest a potential solid link between the FA signaling pathway and pediatric AML. Notably, the pediatric AML patients in cluster 2 or high-risk groups showed a worse survival prognosis.

In addition to conducting internal validation of models, we sought external validation of FA-related models by including independent external data. Due to the absence of high-throughput gene expression data for AML patients at our center, we utilized the BEAT AML data. It is worth noting that the BEAT-AML dataset had limited information on children’s AML. Thus, we refrained from filtering the BETA-AML data. The BEAT AML cohort was stratified into high- and low-risk groups based on our FA Lasso model, and the high-risk group exhibited a worse OS prognosis. Using FA-associated multivariate Cox regression analysis, we discovered that OS demonstrated favorable predictive capability for AML patients in the external validation cohort, particularly for the 1-year survival timeframe. However, we did not observe a statistically significant predictive effect for the 5-year survival period, potentially due to our analysis’s limited data on pediatric AML.

To enhance the predictive accuracy and clinical competence of survival prediction, we build an FA-associated Nomogram by combining the risk score, gender, age, and FAB. The calibration curve of both the training and external validation sets showed a significant overlap between the predicted and observed value lines, indicating strong predictive competence and accurate survival prediction. The findings of the FA model indicate that, along with mutation analysis of specific genes, it is crucial to measure the expression pattern of FA pathway genes in pediatric AML data. Standardization of FA expression detection procedures and continuous optimization of FA-related models will contribute to prognostic assessment and treatment decisions for children with AML. In addition, some patients with FA disease are known to develop tumors [21,32]. Previous studies have shown that Azacitidine effectively treats pediatric patients with FA and AML [20]. It is worth investigating the molecular mechanism underlying the transformation from FA to tumor and conducting specific chemosensitivity analysis. Once sufficient sample information is obtained, this can be achieved by studying the expression and mutation profile of FA-related genes.

The involvement of FA genes in DNA repair is closely linked to genomic maintenance within cells under stress conditions [10,33]. Despite being a rare chromosomal instability disorder [32], the functional loss of the FA signaling pathway during the DNA repair process is crucial for the occurrence and development of certain tumors [17,18,34]. Two components of the FA signaling pathway, namely BRCA1 and BRCA2, function as susceptibility genes for breast cancer [21]. Our study identified five hub prognostic genes in our model: BRIP1, FANCC, FANCL, MAD2L2, and RFWD3. As expected, clustering and risk-related gene enrichment analyses revealed a set of DNA repair-related events, including “nucleotide excision repair” and “homology-directed repair.” Besides, we observed enrichment of the cell cycle events, such as “M_phase,” “cell cycle checkpoints,” and “G2M checkpoint.” These findings suggest that the failure of timely and effective repair of damaged DNA during cell division is a critical factor in carcinogenesis when exposed to harmful external stimuli. Interestingly, we have seen the enrichment of peroxide-related biological metabolic issues, such as the “hydrogen peroxide catabolic process” and “peroxidase activity.” It has been observed that cells of individuals with FA are particularly vulnerable to oxidative stress, which is associated with the FANCG protein in mitochondria and peroxidase activity [35]. These findings suggest that the disruption in the peroxidase metabolic process contributes to the accumulation of oxidative DNA damage during tumorigenesis.

5 Conclusion

Overall, this study employed the expression data of FA-related genes to conduct a tumor clustering analysis. Also, a novel clinical predictive model was established, incorporating five FA-related signatures (BRIP1, FANCC, FANCL, MAD2L2, and RFWD3) for patients diagnosed with AML. Furthermore, a novel FA Nomogram was developed, demonstrating improved validity in predicting clinical survival outcomes. The FA-related prognostic model and tumor clustering have the potential to serve as prognostic predictors, aiding clinicians in evaluating the prognosis of pediatric AML patients.

Abbreviations

AML

acute myeloid leukemia

FA

Fanconi anemia

FAB

French–American–British

OS

overall survival

TCGA

The Cancer Genome Atlas

GEO

gene expression omnibus

PCA

principal component analysis

TPM

transcripts per million

GTEx

genotype-tissue expression

FDR

false discovery rate

FC

fold change

GSEA

gene set enrichment analysis

GO

gene ontology

KEGG

Kyoto Encyclopedia of Genes and Genomes

ROC

receiver operating characteristic

AUC

area under the curve

NRI

net reclassification improvement

IDI

integrated discrimination improvement

DCA

decision curve analysis

Acknowledgments

The authors express their gratitude for the contribution of available online datasets or datasets, such as TARGET, TCGA, GEO, BEAT-AML, and GTEx.

  1. Funding information: This work was supported by grants from the Ministry of Science and Technology of China (2019YFA0110803), the National Natural Science Foundation of China (81500156, 82170135), Tianjin Natural Science Foundation Project (20JCYBJC00470), and the National Key Research and Development Program of China (2018YFA0107801).

  2. Author contributions: L. Chang, X. Cheng, and X. Zhu designed the study. L. Chang, X. Gao, and L. Zhang performed tumor clustering, Lasso regression modeling construction, Cox regression, gene enrichment, and nomogram establishment analyses. L. Chang, X. Gao, and X. Zhu interpreted the data and drafted the manuscript. W. Yuan and Y. Zou reviewed and revised the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Data availability statement: The data used to support the findings of this study are available from the corresponding author upon reasonable request.

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Received: 2023-06-27
Revised: 2023-10-17
Accepted: 2023-10-19
Published Online: 2023-11-09

© 2023 the author(s), published by De Gruyter

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

Artikel in diesem Heft

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  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0847
Schlagwörter für diesen Artikel
Fanconi anemia; acute myeloid leukemia; prognosis; children; expression
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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Heruntergeladen am 8.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0847/html
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