Pyroptosis-related lncRNAs are potential biomarkers for predicting prognoses and immune landscapes in patients with gastric adenocarcinoma

Abstract

Abstract Objectives The purpose of this study was to investigate the significance of pyroptosis-related lncRNAs (PRlncRNA) in predicting prognoses and immune landscapes of patients with gastric adenocarcinoma (STAD). Methods Transcriptomic data and clinicopathological data were obtained from The Cancer Genome Atlas database. Based on correlation analysis and univariate Cox regression, prognostic PRlncRNA were identified. Subsequently, a PRlncRNA prognostic signature (PRLPS) was generated via least absolute shrinkage and selection operator (LASSO) regression, Kaplan–Meier method, receiver operating characteristic (ROC) curves, principal component analysis, and univariate and multivariate regression. Besides, the clinicopathological characteristics, tumor microenvironment (TME) scores, the immune landscapes in different risk subgroups were explored. Moreover, based on three PRlncRNA, we constructed a competing endogenous RNA (ceRNA) network. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) and Gene Ontology (GO) analysis were performed for biological functional analysis based on the difference between high- and low- risk groups, which also used to screen out potential STAD drugs. Results 21 PRlncRNA made up the prognostic signature, which had significant value in predicting the overall survival (OS), clinicopathological features, TME, immune checkpoint genes expression, and the response to immune checkpoint inhibitors of patients with STAD. In a addition, we constructed a ceRNA network comprising 3 PRlncRNAs and 69 mRNAs. The function of PRlncRNA was related to cancer-associated pathways. Ten small molecular drugs that might improve the prognosis of patients were screened out by connectivity maps. Conclusions Using PRlncRNA as a prognostic indicator for STAD, we identified predictive biomarkers and immunotherapy targets while refreshing our understanding.

Keywords

• Gastric adenocarcinoma
• Pyroptosis
• Long non-coding RNAs
• Prognostic signature
• Tumor microenvironment
• Immunotherapy