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

Abstract

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.

Construction of a survival nomogram for gastric cancer based on the cancer genome atlas of m6A-related genes

“…Therefore, the prognosis of GC is of great importance to patients. Currently, although there is a large amount of constructed models to predict the prognosis of GC patients, the variables included were confined, especially the m6A-related genes they incorporated were limited, and other important clinicopathological characteristics such as age, gender, and staging were ignored (Su et al, 2019;Zhang B. et al, 2020;Li et al, 2021;Yue et al, 2022). The AJCC staging system is still the most widely used method to assess the prognosis of patients with GC based on factors such as the location of the primary lesion, tumor size, and the presence of distant metastases (Kumagai and Sano, 2021).…”

Identification of m6A-related long non-coding RNAs for predicting prognosis and immune characterizations in gastric cancer

“…However, significant therapeutic strategies are still needed for the less differentiated histologic subtypes of gastric adenocarcinoma ( Sitarz et al, 2018 ; Joshi and Badgwell, 2021 ). In addition, because of genetic heterogeneity and the absence of novel treatment methods, the prognosis of patients with GC remains dissatisfactory ( Yue et al, 2022 ). Therefore, appropriate therapies should be developed to forecast the survival probability (SP) of GC patients, better detect tumor growth, and enhance treatment results.…”