Characterization of the Prognostic m6A-Related lncRNA Signature in Gastric Cancer

Abstract

N6-methyladenosine (m6A) is a common form of mRNA modification regulated by m6A RNA methylation regulators and play an important role in the progression of gastric cancer (GC). However, the prognostic role of m6A-related lncRNA in gastric cancer has not been fully explored. This study aims at exploring the biological function and prognostic roles of the m6A-related lncRNA signature in gastric cancer. A total of 800 m6A-related lncRNAs were identified through Pearson correlation analysis between m6A regulators and all lncRNAs. Eleven m6A-related lncRNA signatures were identified through a survival analysis and the Kaplan-Meier (KM) curve analysis results suggest that patients in the low-risk group have a better overall survival (OS) and disease-free survival (DFS) outcome than the high-risk group. Also, the lncRNA signature can serve as an independent prognostic factor for OS and DFS. The gene set enrichment analysis (GSEA) result suggests that patients in the high-risk group were mainly enriched in the ECM receptor interaction, focal adhesion, and cytokine-cytokine receptor interaction pathway, while the low-risk group was characterized by the base excision repair pathway. We further constructed an individualized prognostic prediction model via the nomogram based on the independent prognostic factor for the OS and DFS, respectively. In addition, some candidate drugs aimed at GC risk group differentiation were identified using the Connective Map (CMAP) database. Lastly, four subgroups (C1, C2, C3, and C4) were identified based on the m6A-related lncRNA expression, through a consensus clustering algorithm. Among them, C1 and C2 have a greater likelihood to respond to immune checkpoint inhibitor immunotherapy, suggesting that the C1 and C2 subgroup might benefit from immunotherapy. In conclusion, the m6A-related lncRNA signature can independently predict the OS and DFS of GC and may aid in development of personalized immunotherapy strategies.

Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma

“…Jin et al construct an m6A-related signature which could predict the response to immunotherapy in adrenocortical carcinoma (37). Wang et al constructed an m6Arelated lncRNA signature which could discriminate patients with response to immune checkpoint inhibitor in gastric cancer (28).…”

“…Transcriptome profiling data and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov). A list of 23 m6A regulators was obtained from a published article, which include writers (METTL3, METTL14, METTL16, WTAP, VIRMA, RBM15, RBM15B, and ZC3H13), erasers (FTO and ALKBH5), and readers (YTHDC1, YTHDC2, IGF2BP1, IGF2BP2, IGF2BP3, YTHDF1, YTHDF2, YTHDF3, HNRNPC, LRPPRC, HNRNPA2B1, FMR1, and RBMX) (24,28,29). The differential analysis of m6A regulators and m6A genes was obtained using "limma" package in R software.…”

m6A Regulator-Mediated Methylation Modification Model Predicts Prognosis, Tumor Microenvironment Characterizations and Response to Immunotherapies of Clear Cell Renal Cell Carcinoma

“…However, more studies are needed to decipher the diversity of abnormal methylation or recognition abnormality of methylation position and tumor immunophenotype. Determining the role of various m 6 A modification modes in ccRCC microenvironment could improve our understanding of anti-tumor immune response and lay the foundation for personalized treatment of ccRCC patients ( 45 – 47 ).…”

Construction and Characterization of Long Non-Coding RNA-Associated Networks to Reveal Potential Prognostic Biomarkers in Human Lung Adenocarcinoma

“…Results showed that these regulators were mutated in LUAD, although the alteration frequencies were not high (Figure 6A, less than 4%). M6A modifications of lncRNAs were also demonstrated as the powerful evidences in cancer researches (31,32). Studies also found that m6A regulators could trigger lncRNA expression.…”