Prognostic value of RNA methylation-related genes in gastric adenocarcinoma based on bioinformatics.

ABSTRACT

Background: Gastric cancer (GC) is a malignant tumor that originates from the epithelium of the gastric mucosa and has a poor prognosis. Stomach adenocarcinoma (STAD) covers 95% of total gastric cancer. This study aimed to identify the prognostic value of RNA methylation-related genes in gastric cancer. Methods: In this study, The Cancer Genome Atlas (TCGA)-STAD and GSE84426 cohorts were downloaded from public databases. Patients were classified by consistent cluster analysis based on prognosis-related differentially expressed RNA methylation genes Prognostic genes were obtained by differential expression, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses. The prognostic model was established and validated in the training set, test set and validation set respectively. Independent prognostic analysis was implemented. Finally, the expression of prognostic genes was affirmed by reverse transcription quantitative PCR (RT-qPCR). Results: In total, four prognostic genes (ACTA2, SAPCD2, PDK4 and APOD) related to RNA methylation were identified and enrolled into the risk signature. The STAD patients were divided into high- and low-risk groups based on the medium value of the risk score, and patients in the high-risk group had a poor prognosis. In addition, the RNA methylation-relevant risk signature was validated in the test and validation sets, and was authenticated as a reliable independent prognostic predictor. The nomogram was constructed based on the independent predictors to predict the 1/3/5-year survival probability of STAD patients. The gene set enrichment analysis (GSEA) result suggested that the poor prognosis in the high-risk subgroup may be related to immune-related pathways. Finally, the experimental results indicated that the expression trends of RNA methylation-relevant prognostic genes in gastric cancer cells were in agreement with the result of bioinformatics. Conclusion: Our study established a novel RNA methylation-related risk signature for STAD, which was of considerable significance for improving prognosis of STAD patients and offering theoretical support for clinical therapy.