Identification of Five N6-Methylandenosine-Related ncRNA Signatures to Predict the Overall Survival of Patients with Gastric Cancer

DISEASE MARKERS(2022)

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摘要
Noncoding ribonucleic acids (ncRNAs) are involved in various functions in the formation and progression of different tumors. However, the association between N6-methyladenosine-related ncRNAs (m6A-related ncRNAs) and gastric cancer (GC) prognosis remains elusive. As such, this research was aimed at identifying m6A-related ncRNAs (lncRNAs and miRNAs) in GC and developing prognostic models of relevant m6A-related ncRNAs and identifying potential biomarkers regulated by m6A. In this study, the m6A2Target database, Starbase database, and The Cancer Genome Atlas (TCGA) were used to screen m6A-related ncRNAs. And then, we performed integrated bioinformatics analyses to determine prognosis-associated ncRNAs and to develop the m6A-related ncRNA prognostic signature (m6A-NPS) for GC patients. Finally, five m6A-related ncRNAs (including lnc-ARHGAP12, lnc-HYPM-1, lnc-WDR7-11, LINC02266, and lnc-PRIM2-7) were identified to establish m6A-NPS. The predictive power of m6A-NPS was better in the receiver operating characteristic (ROC) curve analysis of the training set (area under the curve (AUC), >0.6). The m6A-NPS could be utilized to classify patients into high- and low-risk cohorts, and the Kaplan-Meier analysis indicated that participants in the high-risk cohort had a poorer prognosis. The entire TCGA dataset substantiated the predictive value of m6A-NPS. Significant differences in TCGA molecular GC subtypes were observed between high- and low-risk cohorts. The ROC curve analysis indicated that m6A-NPS had better predictive power than other clinical characteristics of GC prognosis. Uni- and multivariate regression analyses indicated m6A-NPS as an independent prognostic factor. Furthermore, the m6A status between the low-risk cohort and high-risk cohort was significantly different. Differential genes between them were enriched in multiple tumor-associated signaling pathways. In summary, five m6A-related ncRNA signatures that could forecast the overall survival of patients with GC were identified.
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