Recognition of DNA Methylation Molecular Features for Diagnosis and Prognosis in Gastric Cancer

Abstract

Background: The management of gastric cancer (GC) still lacks tumor markers with high specificity and sensitivity. The goal of current research is to find effective diagnostic and prognostic markers and to clarify their related mechanisms.Methods: In this study, we integrated GC DNA methylation data from publicly available datasets obtained from TCGA and GEO databases, and applied random forest and LASSO analysis methods to screen reliable differential methylation sites (DMSs) for GC diagnosis. We constructed a diagnostic model of GC by logistic analysis and conducted verification and clinical correlation analysis. We screened credible prognostic DMSs through univariate Cox and LASSO analyses and verified a prognostic model of GC by multivariate Cox analysis. Independent prognostic and biological function analyses were performed for the prognostic risk score. We performed TP53 correlation analysis, mutation and prognosis analysis on eleven-DNA methylation driver gene (DMG), and constructed a multifactor regulatory network of key genes.Results: The five-DMS diagnostic model distinguished GC from normal samples, and diagnostic risk value was significantly correlated with grade and tumor location. The prediction accuracy of the eleven-DMS prognostic model was verified in both the training and validation datasets, indicating its certain potential for GC survival prediction. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The prognostic risk score was an independent risk factor for the prognosis of GC, which was significantly correlated with N stage and tumor location, positively correlated with the VIM gene, and negatively correlated with the CDH1 gene. The expression of CHRNB2 decreased significantly in the TP53 mutation group of gastric cancer patients, and there were significant differences in CCDC69, RASSF2, CHRNB2, ARMC9, and RPN1 between the TP53 mutation group and the TP53 non-mutation group of gastric cancer patients. In addition, CEP290, UBXN8, KDM4A, RPN1 had high frequency mutations and the function of eleven-DMG mutation related genes in GC patients is widely enriched in multiple pathways.Conclusion: Combined, the five-DMS diagnostic and eleven-DMS prognostic GC models are important tools for accurate and individualized treatment. The study provides direction for exploring potential markers of GC.

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

“…In addition, in multiple cancers, DNA methylation throughout the genome is an epigenetic modification contributing to the regulation of cancer-associated genes ( Liu D et al, 2021 ; Rogozin et al, 2021 ). Research studies have verified that PDK4 methylation could display the oncogenic roles in colon cancer ( Leclerc et al, 2017 ).…”

Comprehensive analyses of cuproptosis-related gene CDKN2A on prognosis and immunologic therapy in human tumors

“…Numerous types of research have indicated that DNA methylation, as an epigenetic modification, contributed to regulating the expression of cancer-related genes. [ 31 ] Thus, the promoter methylation level of CDKN2A between tumors and normal tissues was explored via the “CPTAC” dataset. As displayed in Figure 6 A, compared with normal samples, the promoter methylation level of CDKN2A was dramatically increased in most cancers (e.g., BLCA, COAD, KIRC, LIHC, and so on), except KIRP with decreased methylation level.…”

“…As an epigenetic modification, DNA methylation contributes to regulating the expression of cancer-related genes. [ 31 ] A meta-analysis performed by Zhou pointed out that CDKN2A methylation had a crucial role in the occurrence of esophageal cancer. [ 41 ] However, Cao et al indicated that CDKN2A methylation was not significantly correlated with the progression of PRAD.…”

Prognostic significance of JAM 3 in gastric cancer: An observational study from TCGA and GEO

“…More and more corroboration alludes to a crucial role for aberrant DNA methylation in the initiation and development of GC. [25][26][27][28] To begin our investigation, we used Pearson coefficients to see if the JAM3 methylation status affected JAM3 mRNA expression. In GC tissues, a strong inverse connection was seen between JAM3 methylation and JAM3 mRNA expression.…”