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Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development

  • Muhammad Naveed EMAIL logo , Muhammad Saad Mughal , Tariq Aziz , Syeda Izma Makhdoom , Hamza Jamil , Ayaz Ali Khan EMAIL logo , Nawal Al-Hoshani , Fakhria A. Al-Joufi , Roaa Mohammed Tahir Kassim and Maher S. Alwethaynani
Published/Copyright: March 26, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, emphasizing the need for improved prognostic biomarkers. Recent studies have identified the mRNA-modifying METTL3 oncogene as a potential biomarker in CRC progression.

Objective

This study aimed to investigate the expression patterns of METTL3 in CRC, assess its association with clinical outcomes, identify interacting proteins and biological pathways, and explore its correlation with immune cell infiltration.

Methods

Comprehensive analyses were conducted using public datasets, including transcriptome profiles from The Cancer Genome Atlas and the GSE103512 dataset. Protein–protein interaction (PPI) networks, pathway enrichment, and immune infiltration analyses were performed to elucidate METTL3’s role in CRC progression.

Results

METTL3 expression was significantly higher in CRC tissues compared to normal tissues (p < 0.001). Mutations in METTL3 were detected in approximately 6% of CRC cases, with fusion events involving the SRPK2 gene. PPI analysis identified ten interacting proteins, including METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429. METTL3 expression showed a positive correlation with METTL4, METTL14, NCBP1, and WTAP expression (R > 0.5, p < 0.001). Higher METTL3 expression was associated with immunosuppressive phenotypes, such as increased infiltration of tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts (p < 0.001). Pathway enrichment analysis revealed METTL3’s involvement in crucial pathways, including the cell cycle and renal cell carcinoma (p < 0.01). Gene ontology analysis highlighted its role in mRNA and RNA-related processes.

Conclusion

The study supports the potential of METTL3 as a prognostic biomarker in CRC and highlights its involvement in immune modulation and cancer progression. These findings lay the groundwork for future studies aimed at developing targeted therapies and improving patient outcomes.

Graphical abstract

Keyword: colorectal; RMGs; biomarker; enrichment; immune cells; mutation; interaction

1 Introduction

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, and its prognosis remains a major concern. Over the years, researchers have focused on identifying novel biomarkers that can improve early detection and prognostic prediction of CRC [1]. In recent studies, an emerging mRNA-modifying METTL3 oncogene has garnered significant attention as a potential prognostic biomarker in the progression of CRC. This exciting development holds promise for revolutionizing the diagnosis, treatment, and management of this devastating disease [2,3]. According to the National Cancer Institute, the colon, which is the longest portion of the large intestine, and/or the rectum can both develop cancer (the last several inches of the large intestine before the anus). The frequency of colon and rectal cancer, which are prevalent malignant tumors of Aden epithelial origin, rises with age [4].

Between 2014 and 2018, the number of new cases of CRC in Americans over 50 years of age declined slightly yearly, but instances in Americans under 50 years of age significantly rose yearly [5]. Deaths from CRC decreased annually from 2015 to 2019 by a little amount. Men are diagnosed with CRC more frequently than women. The METTL3 oncogene belongs to the METTL family of proteins and plays a crucial role in RNA methylation, a post-transcriptional modification process involved in gene expression regulation [6]. Recent investigations have revealed aberrant expression and dysregulation of METTL3 in CRC, indicating its potential involvement in tumor progression. By catalyzing the addition of a methyl group to RNA molecules, METTL3 influences mRNA stability, translation efficiency, and splicing patterns, ultimately impacting gene expression networks that drive cancer development [7].

Early studies have shown that aberrant METTL3 expression levels correlate with clinical features such as tumor stage, metastasis, and overall survival rates in CRC patients [8]. These findings suggest that METTL3 could serve as a reliable indicator of disease progression and patient outcomes. By identifying and monitoring METTL3 expression patterns, clinicians may be able to make more informed decisions regarding treatment strategies, allowing for personalized therapies tailored to individual patients [9]. Transcriptomics has potential as a new method for accurately classifying cancer. In mammalian cells, gene expression silencing is a method of controlling transcription [10]. The process is carried out via RNA interference (RNAi), in which a short noncoding RNA joins an RNA-induced silencing complex and subsequently cleaves target mRNAs. Oncogenes and other driver genes important in cancer cell proliferation, the cell cycle, and tumor growth can be silenced by RNAi-mediated gene silencing, making it an interesting method for application in cancer treatment [11]. In this line, clinical trials are now assessing the therapeutic benefit from the use of short-interfering RNA-based therapies in cancer patients [12].

DKC1 promotes the growth of CRC by stabilizing and binding to the mRNA of some ribosomal proteins in a manner that is reliant on its pseudo uridine synthase activity [13,14]. In this case, uridine is isomerized, resulting in the ribose being linked to C5 rather than the usual N1 in the process. Up to 100 pseudo uridine (“psi”) residues can be found in each rRNA; these residues may help to keep the structure of rRNAs stable, necessary for the preservation of telomeres and ribosome biosynthesis [15]. In addition, YTHDF1 promotes both the ability for metastasis and proliferation of human colorectal cancer cells. It promotes the degradation of mRNAs that contain the amino acid m6A by interacting with the CCR4-NOT complex, acting as a regulator of mRNA stability. A number of genetic, epigenetic, and epitranscriptomic changes contribute to the development of colorectal tumors. The most prevalent messenger RNA (mRNA) modification in humans is RNA N6-methyladenosine (m6A), which plays a crucial role in posttranscriptional regulation of mRNA splicing, translation, and destruction [16].

The METTL3-METTL14 heterodimer, an N6-methyltransferase complex, affects a number of functions, including the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, T-cell differentiation, and initial miRNA processing [17]. The mechanistic role of METTL3 in CRC progression could unveil new therapeutic targets and strategies. Researchers are actively investigating the downstream effects of METTL3 dysregulation, exploring its impact on specific signaling pathways and biological processes that contribute to cancer growth and metastasis. By elucidating these mechanisms, scientists hope to develop targeted therapies that can modulate METTL3 expression or its downstream effects, providing new avenues for treatment and potentially improving patient outcomes [18].

The aim of this study was to investigate the mRNA-modifying METTL3 oncogene as a potential prognostic biomarker in CRC. The study employed a comprehensive approach that involved data collection from public repositories, differential expression analysis using transcriptome profiles from The Cancer Genome Atlas (TCGA) and GSE103512 datasets, gene expression analysis, protein–protein interaction (PPI) network analyses, mutation and correlation analyses, evaluation of METTL3’s role in immunosuppressive cells, and improvements in the quality of potential genes and pathways. By conducting these steps, the study aimed to determine the expression patterns of METTL3 in CRC, assess its association with clinical outcomes, identify potential interacting proteins and biological pathways, and explore its correlation with immune cell infiltration. The findings from this study would contribute to understanding the significance of METTL3 as a prognostic biomarker and its potential implications in CRC prognosis and treatment.

2 Materials and methods

2.1 Data collection

The keywords “RNA modification” were used to find the RMGs in PubMed. The datasets GSE103512 and TCGA, as well as the transcriptome profiles, were downloaded from Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gCOADREAD/gds). The following analyses were conducted using 715 COADREAD and 15 normal cases in TCGA and a total of 64 COADREAD and 18 normal cases in GSE103512.

2.2 Differential expression analysis

The differentially expressed genes were found using the GEO2R, an interactive web tool that enables users to examine the gene expression between various groups of samples in a GEO dataset (DEGs). To examine TCGA expression profile of CRC, the R package “Deseq2” is used. The cut-off parameters for excluding DEGs were |log2FC| > 1 and a p value of 0.05. Table S1 contains a list of the DEGs from the two datasets. Then, using Venny 2.1, the RMGs and DEGs that overlapped between GSE103512 and TCGA were chosen and used for additional analysis.

2.3 Gene expression analysis using TCGA and GEO datasets

TCGA and GSE103512 expression profiling data were used to conduct the METTL3 expression study. The efficacy of the expression level of any gene of interest in differentiating between COADREAD and healthy samples was then assessed using the webserver UALCAN (http://ualcan.path.uab.edu/index.html).

2.4 PPI network analyses

The functional PPIs of METTL3 were found using the STRING database, which can predict and analyze functional interactions between proteins. Gene networks embracing METTL3 were found using GeneMANIA (http://genemania.org/).

2.5 METTL3 mutation and correlation analyses

Using cBioPortal (https://www.cbioportal.org/), the METTL3 mutation was carried out. Based on TCGA data, the GEPIA (Gene Expression Profiling Interactive Analysis) database (http://gepia.cancer-pku.cn/) was used to evaluate the METTL3-associated genes.

2.6 Evaluation of METTL3’s role in immunosuppressive cells

TIMER (https://cistrome.shinyapps.io/timer/) is a web-based program used in the study of the interplay between various cancers and the immune system. Using many gene markers for immune cell infiltration, we found that METTL3 expression correlated with tumor infiltration by diverse immune cells. Multiple genetic markers were used to make this connection. The purity-adjusted partial Spearman’s rho value can be used to measure the strength of the association between immune cells and genes; a p-value of 0.05 indicates statistical significance.

2.7 Improvements in the quality of potential genes and pathways

We used gene set enrichment analysis (GSEA) to identify potential biological pathways involving METTL3. The study of the enriched gene set was judged significant when the nominal p-value was less than 0.01 and the false COADREAD rate (FDR) q-value was less than 0.05. cBioPortal study revealed that 16149 genes had a positive connection with METTL3 (R > 0.3, p < 0.05), and these genes were used in the BP, CC, and MF studies. In light of these results, bubble diagrams were made using the “ggplot2” R Studio tool to display the findings of the BP, CC, and MF investigations.

3 Results

3.1 COADREAD DEGs-RMGs TCGA and GEO data

From PubMed, we selected a total of 6 RMGs. The GEO and UCSC Xena databases were mined for CRC in GSE103512 cohorts and TCGA AffyU133a expression profiles. Figure 1a displays DEGs obtained using GEO2R and R package “Deseq2” analyses between COADREAD and normal samples, and a total of 16,149 and 44,171 DEGs were obtained in TCGA dataset and the GSE103512 dataset, respectively (Table S1). By comparing the RMGs and DEGs from both groups, we were able to locate diagnostic biomarkers that could be employed across both groups. DKC1, YTHDF1, and METTL3 were thus identified as RMGs according to their differential expression (Figure 1b). Due to the fact that DKC1 and YTHDF1 revealed contrasting patterns of expression in CRC (COADREAD) and normal tissues in TCGA and GSE103512 (Figure 1c). However, METTL3 consistently showed higher expression in COADREAD than in normal cases, indicating diagnostic potential.

Figure 1 The identification of DEGs-RMGs using COADREAD data in TCGA and GEO. (a) and (b) The volcano plot of DEGs in GSE103512 and TCGA data. (c) DKC1, YTHDF1, and METTL3 were identified as the overlapping genes of DEGs in both datasets.
Figure 1

The identification of DEGs-RMGs using COADREAD data in TCGA and GEO. (a) and (b) The volcano plot of DEGs in GSE103512 and TCGA data. (c) DKC1, YTHDF1, and METTL3 were identified as the overlapping genes of DEGs in both datasets.

3.2 METTL3 in CRC: Mutation analysis

A mutation study of METTL3 in cBioPortal revealed the fusion of METTL3 with SRSF Protein Kinase 2 (SRPK2) in serous CRC, which was expected given the association between mutations in RNA modification genes and numerous forms of human malignancies (Table 1). The mutation rate in the METTL3 is around 6% (Figure 2a). The mutation in METTL3 is in the region of MT-A70 and the diseases associated with the mutation in METLL3 include colon adenocarcinoma, rectal adenocarcinoma, and rectum adenocarcinoma (Figure 2b).

Table 1

The mutation distribution of METTL3 in ovarian cancer according to cBioPortal

Study of origin Sample ID Cancer type detailed Protein change Mutation type Variant type Copy no.
CRC TCGA-AD-6889-01 Colon adenocarcinoma Y569C Missense SNP Diploid
CRC TCGA-G4-6309-01 Colon adenocarcinoma T106M Missense SNP Diploid
CRC TCGA-A6-3807-01 Colon adenocarcinoma D114G Missense SNP ShallowDel
CRC TCGA-AA-3989-01 Colon adenocarcinoma Y406C Missense SNP ShallowDel
CRC TCGA-AA-3864-01 Colon adenocarcinoma R415C Missense SNP Diploid
CRC TCGA-AG-A002-01 Rectal adenocarcinoma L533S Missense SNP Diploid
CRC TCGA-CM-4747-01 Colon adenocarcinoma R25S Missense SNP ShallowDel
CRC TCGA-WS-AB45-01 Mucinous adenocarcinoma of the colon and rectum R379C Missense SNP Diploid
Figure 2 Mutation analysis in METTL3 gene. (a) Mutation type, spectrum, and genetic alteration in METTL3 gene. (b) DKC1, YTHDF1, and METTL3 were identified as the overlapping genes of DEGs in both datasets.
Figure 2

Mutation analysis in METTL3 gene. (a) Mutation type, spectrum, and genetic alteration in METTL3 gene. (b) DKC1, YTHDF1, and METTL3 were identified as the overlapping genes of DEGs in both datasets.

3.3 METTL3-interacting network

METTL3 and its partner’s PPI and gene networks were analyzed using the String and GeneMANIA programs. According to the results of the PPI research, METTL3 interacts with ten different proteins, including METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429 as shown in Figure 3a. Twenty genes (METTL14, WTAP, METTL4, GTF2F2, POLR2D, RBM15B, GTF2F1, POLR2C, POLR2B, POLR2J, NCBP2, POLR2I, METTL17, NCBP1, LUC7L3, POLR2G, POLR2H, POLR2E, POLR2K, and SDR39U1) were found in the GeneMANIA analysis to be physically or genetically associated with METTL3 (Figure 3b). Four genes (METTL14, METTL4, NCBP1, and WTAP) were found to be common in both PPI and gene interaction (Figure 3c). Furthermore, GEPIA analysis demonstrated a strong correlation between METTL3 expression and that of METTL4 (R = 0.59, p = 6. 09 × 10−5), METTL14 (R = 0.54, p = 0), NCBP1 (R = 0.69, p = 1 × 10−9), and WTAP (R = 0.82, p = 0) as shown in Figure 3d.

Figure 3 The interaction network and correlation of PUS7. (a) The protein interaction network of PUS7. Ten proteins METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429 physically/functionally interact with PUS7. (b) Twenty genes named METTL14, WTAP, METTL4, GTF2F2, POLR2D, RBM15B, GTF2F1, POLR2C, POLR2B, POLR2J, NCBP2, POLR2I, METTL17, NCBP1, LUC7L3, POLR2G, POLR2H, POLR2E, POLR2K, and SDR39U1 have physical interactions or genetic interactions, share protein domains with METTL3. (c) Four genes (METTL14, METTL4, NCBP1, and WTAP) were shared by the two networks. (d) The correlation analysis of METTL3 with METTL14, METTL4, and NCBP1.
Figure 3

The interaction network and correlation of PUS7. (a) The protein interaction network of PUS7. Ten proteins METTL4, EIF3H, RBM15B1, CBLL1, WTAP, NCBP1, RBM15, ZC3H13, METTL14, and KIAA1429 physically/functionally interact with PUS7. (b) Twenty genes named METTL14, WTAP, METTL4, GTF2F2, POLR2D, RBM15B, GTF2F1, POLR2C, POLR2B, POLR2J, NCBP2, POLR2I, METTL17, NCBP1, LUC7L3, POLR2G, POLR2H, POLR2E, POLR2K, and SDR39U1 have physical interactions or genetic interactions, share protein domains with METTL3. (c) Four genes (METTL14, METTL4, NCBP1, and WTAP) were shared by the two networks. (d) The correlation analysis of METTL3 with METTL14, METTL4, and NCBP1.

3.4 Immunosuppressive properties in COADREAD tissues are associated with overexpression of METTL3

Here, we used TCGA cohorts to investigate whether high levels of COADREAD mRNA expression were associated with immunosuppressive cell infiltrations into tumors. We found an unexpected negative correlation between METTL3 mRNA expression levels and tumor purity (Figure 4a). High levels of METTL3 expression also correlate highly (all p < 0.001, cor > 0.3) with the infiltration levels of tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts in bladder and prostate cancer cohorts. Conversely, it was discovered that the number of CD8+ T cells, a kind of antitumor T cell, infiltrated a tumor was inversely correlated with the number of METTL3 mRNA copies (all p < 0.001, cor < 0) (Figure 4b). Combined, these data strongly suggested that increased METTL3 expression, via a mechanism involving T-cell exclusion, is associated with immunosuppressive phenotypes in COADREAD tissues.

Figure 4 Immune infiltration analysis of METTL3 gene within the tumor microenvironment (TME) of colon adenocarcinoma. (a) Expression level of different immune cells in COADREAD cancer. (b) Copy number of immune cells in READ only.
Figure 4

Immune infiltration analysis of METTL3 gene within the tumor microenvironment (TME) of colon adenocarcinoma. (a) Expression level of different immune cells in COADREAD cancer. (b) Copy number of immune cells in READ only.

3.5 CRC: Pathway enrichment analysis of METTL3

A GSEA pathway analysis was carried out to investigate possible METTL3-related activities and regulatory processes in CRC. In CRC, METTL3 is involved in six distinct pathways. Natural killer cell-mediated cytotoxicity, cell division, cancer, renal cell carcinoma, blood-forming stem cells, and PPAR signaling pathways are major pathways (Figure 5). Cell cycle, renal cell carcinoma, and pathways that are included in cancer stand out as two of the most crucial processes associated with the growth of CRC cells, among many others. These findings suggest that METTL3 COADREAD expression in CRC may enhance tumor growth by modulating cell cycle progression and DNA replication.

Figure 5 Top six pathway enrichment analyses of METTL3 in CRC.
Figure 5

Top six pathway enrichment analyses of METTL3 in CRC.

3.6 Analyses of METTL3 GO terms in CRC

A total of 16,149 genes positively related to METTL3 (R > 0.3, p < 0.0001) according to TCGA CRC data through the cBioPortal database were analyzed using R software, package “ggplot2” to further elucidate the GO enrichment analysis as shown in Figure 6. METTL3 was found to play a major role in a variety of processes including fatty acid metabolism, mRNA methylation, RNA methylation, regulation of mRNA 3′ end processing, forebrain radial glial cell differentiation, and RNA and mRNA binding.

Figure 6 GO enrichment analysis of METTL3.
Figure 6

GO enrichment analysis of METTL3.

4 Discussion

CRC is the third greatest cause of cancer-related death in the United States overall and the second leading cause among both men and women when data for both sexes are considered [18]. About 52,580 deaths are expected to occur in 2022 as a result. Too often, ovarian cancer is diagnosed after the disease has progressed significantly. The molecular pathways driving COADREAD metastases must be better understood before effective therapeutic options may be developed [19]. There are many obstacles in the way of effective treatment for this type of cancer, one of which is the search for diagnostic biomarkers. Researchers have found that most anti-cancer medications are cytotoxic, or destructive to all cells. Therefore, it is vital to develop a highly accurate diagnostic marker for COADREAD to enhance clinical diagnosis and raise the possibility of a longer life duration. Variations in RNA have been linked to a wide variety of human disorders, cancer included [20]. We used the RMG approach to identify the METTL3 gene as a possible biomarker for CRC because there is currently no established biomarker for this disease [8]. In stem cells, METTL3-mediated pseudouridylation may “activate” some short RNAs produced from tRNAs to control protein synthesis and cell fate [21].

Our investigation into the deregulation of RMGs in CRC led us to METTL3, which is a one-of-a-kind potential biomarker for the detection of COADREAD [22]. We discovered the METTL3 biomarker as a result of our research. This study has substantial clinical implications for the screening, prognosis, diagnosis, and staging of the disease in addition to treatment. The examination of gene expression reveals that patients with CRC (Sinicrope, 2022) had a higher level of METLL3 expression in comparison to healthy controls [23,24]. This validation adds credence to the concept of using METLL3 as a biomarker for the early diagnosis and prognostication of illness [25].

Tumor invasion, cancer growth, and the host immune response all rely on the intricate and ever-changing interactions between immune cells, the stoma, and cancer cells within the TME. Our study of immune infiltrating cells within the TME of the COADREAD tumor led us to the conclusion that high levels of METLL3 expression are correlated with high numbers of tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts [6]. Tumors acquire an invasive character and T-cell exclusion as a result of immunosuppressive cells’ ability to dampen the activity of cytotoxic lymphocytes. Instead, we found a negative correlation between CD8+ T-cell immunological infiltration and METTL3 mRNA expression, which suggests that elevated METTL3 expression is associated with immunosuppressive features in COADREAD tissue via a mechanism involving T-cell exclusion [9].

Analysis of METTL3 as a prognostic biomarker in CRC has recently received extensive focus considering its various functions in tumorigenesis. Our study differs from previous works by using a multi-step approach which involves analyzing transcriptome data from TCGA and GSE103512 datasets, thereby leveraging on TIMER and GEPIA bioinformatics tools. Overall, this integration of multiple datasets and experimental methods can provide a better view of METTL3 in CRC development, immune infiltration, and the associated pathway enrichment, which are not well investigated in previous studies applying only individual dataset or single experimental approach [26].

Prior studies have only examined METTL3’s broad function in RNA methylation and its relevance in different cancers, such as lung and breast cancer. For example, Chen et al. showed that METTL3 contributed to CRC cell nutrition (GLUT1 Canal) and mTORC1 signal activation, making METTL3 a potential prognosis marker of CRC patients [27,28,29]. However, these studies rarely investigated the immune modulation functions of METTL3 in the TME, which is important for CRC progression. However, our results focus on the association between METTL3 and immunosuppressive subtypes, including TAM and Tregs, thus shedding new light on METTL3 as an immunosuppressive factor for CRC [30].

In the past, METTL3 has never been linked to colon cancer. We investigated METTL3’s interaction partners to learn more about its function in COADREAD and how it promotes tumor detection, carcinogenesis, and growth [31,32]. NCBP1 (Nuclear Cap Binding Protein Subunit 1) is a recently confirmed protein-coding gene that has been connected to a wide variety of diseases, including lung cancer. It is interconnected with the FGFR2 signaling in disease pathway and the mRNA splicing minor pathway. PPI and gene network analyses revealed novel interaction partners for METTL3 in CRC, none of which had been described before. WTAP (WT1-associated protein) has been associated with Wilms tumors 1 and 5; however, no evidence has been found linking WTAP to cancer, indicating the unique nature of this protein interaction. The GSEA pathway study revealed that METTL3 mainly regulates the cell cycle, renal cell carcinoma, and cancer pathways, which shed light on the METTL3 signaling mechanism in CRC. These findings suggest that METTL3 promotes the development of CRC by regulating pathways and the cell cycle. Still, further research is needed to verify this hypothesis.

The next steps in the study of METTL3 should lie in experimental and clinical applications of the bioinformatics data obtained. First, in vitro and in vivo experiments should confirm METTL3-regulated immune modulation and the identity of interacting TICs. Further mechanistic investigations are required to define the down-stream effects of METTL3 on immune cell recruitment and activity within the TME [33]. In addition, understanding the relationship between METTL3 and its reported protein targets in this list is relevant to CRC treatment (e.g., WTAP, METTL14) should be further investigated. Due to the increase in METTL3 research focusing on ovarian cancer, extending the study on METTL3 to other cancers that have similar immunosuppressive microenvironments would provide similar information for comparison [34,35]. Further, methods of functional genomics studying METTL3 may be enhanced by existing technologies like new-generation CRISPR-Cas9 gene editing and single-cell RNA sequencing. Preliminary identification of METTL3 small molecule inhibitors or RNA-based therapies may therefore open up new therapeutic avenues.

5 Conclusions

According to the findings of this study, METTL3 is a novel RNA and protein biomarker for CRC that has the potential to be very beneficial. Further study has shown that METTL3, along with METTL4, METTL14, NCBP1, and WTAP, may interact to impact cell cycle, renal cell carcinoma, and pathways that are included in cancer and hence may influence CRC growth. The findings of the aforementioned investigations led to this discovery.

  1. Funding information: The authors greatly acknowledge and express their gratitude to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2025R437), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

  2. Author contributions: Conceptualization, Muhammad Naveed; methodology, Muhammad Saad Mughal; software, Syeda Izma Makhdoom validation, Hamza Jamil; formal analysis; Tariq Aziz; investigation, Syeda Izma Makhdoom and Hamza Jamil; resources, Muhammad Naveed; data curation, Tariq Aziz; writing – original draft preparation, Ayaz Ali Khan; writing – review and editing, Nawal Al-Hoshani, Fakhria A. Al-Joufi, Roaa Mohammed Tahir Kassim, and Maher S. Alwethaynani; visualization, Tariq Aziz; supervision, Muhammad Naveed and Ayaz Ali Khan; project administration, Muhammad Naveed; funding acquisition, Tariq Aziz.

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

  4. Data availability statement: The datasets analyzed during the current study are publicly available. Transcriptomic data were obtained from TCGA (https://portal.gdc.cancer.gov/) and the GEO under accession number GSE103512 (https://www.ncbi.nlm.nih.gov/geo/). All relevant data used in this study are included in the manuscript and its supplementary materials. Further details can be provided by the corresponding author upon reasonable request.

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Received: 2024-04-19
Revised: 2025-02-21
Accepted: 2025-02-25
Published Online: 2025-03-26

© 2025 the author(s), published by De Gruyter

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

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https://doi.org/10.1515/med-2025-1167
Keywords for this article
colorectal; RMGs; biomarker; enrichment; immune cells; mutation; interaction
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
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  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Review Articles
  156. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  157. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  158. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  159. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  160. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  161. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  162. The application of augmented reality in robotic general surgery: A mini-review
  163. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  164. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  165. Plant polyphenols, terpenes, and terpenoids in oral health
  166. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  167. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  168. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  169. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  170. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  171. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  172. Giant borderline ovarian tumours – review of the literature
  173. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  174. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  175. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  176. Supplement strategies for infertility in overweight women: Evidence and legal insights
  177. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  178. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  179. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  180. Strategies for hyperkalemia management in dialysis patients: A systematic review
  181. C-reactive protein-to-albumin ratio in peripheral artery disease
  182. Case Reports
  183. Delayed graft function after renal transplantation
  184. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  185. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  186. Giant right atrial hemangioma presenting with ascites: A case report
  187. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  188. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  189. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  190. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  191. Rapid Communication
  192. Biological properties of valve materials using RGD and EC
  193. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  194. Letter to the Editor
  195. Role of enhanced external counterpulsation in long COVID
  196. Expression of Concern
  197. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  198. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  199. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  200. Corrigendum
  201. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  202. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  203. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  204. Retraction
  205. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  206. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  207. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  208. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  209. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  210. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  211. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  212. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  213. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  214. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  215. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  216. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  217. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  218. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  219. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  220. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  221. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  222. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  223. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  224. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  225. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  226. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  227. A review of brain research on T2DM-related cognitive dysfunction
  228. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  229. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  230. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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