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Gene Signatures and Prognostic Values of N6-Methyladenosine Related Genes in Ovarian Cancer.

ABSTRACT: N6-Methyladenosine (m⁶A) is one of the most prominent modification regulating RNA processing and metabolism. Increasing studies have illuminated the vital role of m⁶A methylation in carcinogenesis. However, little is known about the interaction between m⁶A-related genes and survival of ovarian cancer (OC) patients. The purpose of this study was to obtain more reliable m⁶A-related genes that could be used as prognostic markers of OC using bioinformatics analysis performed on the RNA-seq data of OC. Gene expression datasets of all m⁶A-related genes as well as corresponding clinical data were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. We detected differential expressed m⁶A-related candidate genes as well as their relationship and interaction. m⁶A RNA methylation regulator ALKBH5 and 35 m⁶A-related genes are dysregulated in OC. A gene set that could be used as a potential independent prognostic risk feature was further screened including NEBL, PDGFRA, WDR91, and ZBTB4. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. We applied consensus clustering analysis on the expression of the four prognostic genes and obtained four OC subgroups TM1-TM4. There were significant differences in age, stage and grade among the subgroups, and the overall survival (OS) as well as Disease-free survival (DFS) of TM2 group were shorter than those of the other three groups. Further GO and KEGG enrichment analysis indicated that these differential genes were closely related to biological processes and key signaling pathways involved in OC. In summary, our study has indicated that m⁶A-related genes are key factors in the progression of OC and have potential effects on the prognostic stratification of OC and the development of treatment strategies.

SUBMITTER: Na Z

PROVIDER: S-EPMC8416414 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79-0.91), 0.84 (95%CI: 0.79-0.90) and 0.80 (95%CI: 0.71-0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients.

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Gene Signatures and Prognostic Values of N6-Methyladenosine Related Genes in Ovarian Cancer.

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