Identification of pyroptosis-related lncRNAs as potential prognostic biomarkers in patients with adenocarcinoma of the esophagogastric junction

Abstract

Background Adenocarcinoma of esophagogastric junction (AEG) is a high-mortality gastrointestinal cancer lacking effective prognostic markers. Pyroptosis, a form of programmed cell death, is vital in inflammation and immune response. However, the prognostic role of pyroptosis-related lncRNA in AEG has not been explored.Methods Clinical information and gene expression data for AEG were obtained from The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) was used to narrow down candidate lncRNAs and develop the pyroptosis-related lncRNA risk model. Kaplan-Meier analysis, Multivariate Cox regression, and nomogram were used to assess the risk model. Functional enrichment analysis was used to reveal potential pathways in AEG. The ESTIMATE, TIMER, XCELL, CIBERSORT, ssGSEA, and EPIC algorithms were used to investigate the immune status in different risk groups. The oncoPredict R package was used to identify candidate drugs.Results Pearson correlation analysis identified 816 pyroptosis-related lncRNAs, from which three prognostic lncRNAs (LINC01537, CTD-2033D15.2, ENTPD1-AS1) were selected to construct a risk model using LASSO Cox regression analysis. Kaplan-Meier curve analysis revealed that patients with low-risk scores had superior overall survival (OS) compared to those in the high-risk groups (HR = 1.86, 95% CI 1.21–2.87, p = 0.004). Multivariate analysis demonstrated that the 3 prognostic lncRNA risk score was an independent prognostic factor with a significant predictive value for AEG. A low-risk score indicated an increased infiltration of activated memory CD4 + T cells and was associated with pathways such as DNA replication, cell cycle, mismatch repair, aminoacyl-tRNA biosynthesis, and seleno amino acid metabolism. Additionally, a low-risk score was associated with increased sensitivity to Paclitaxel and KRAS (G12C) inhibitor drugs.Conclusion These results provide new insights into the potential use of the proposed pyroptosis-related lncRNA signature as a prognostic tool and potential therapeutic targets for AEG.