A risk model based on autophagy-related lncRNAs for predicting prognosis and efficacy of immunotherapy and chemotherapy in gastric cancer patients

Abstract

Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNAs essential to the occurrence and development of gastric cancer (GC). We aimed to identify critical lncRNA pairs to construct a prognostic model and assess its performances in prognosis and efficacy prediction in GC patients receiving immunotherapy and chemotherapy. We searched transcriptome and clinical data of GC patients from The Cancer Genome Atlas (TCGA) database. Autophagy-related lncRNAs were identified using co-expression network analysis, and lncRNA pairs with prognostic value were selected using pairwise transcriptome analysis. The gene pairs were subjected to LASSO algorithm for identification of optimal gene pairs for risk model construction. Patients were classified into the low-risk and high-risk groups with the RiskScore as a cutoff. Finally, 9 optimal gene pairs were identified in the LASSO algorithm model for construction of a lncRNA prognostic risk model. For predictive performances, it successfully predicted a shorter survival of high-risk patients than that obtained in low-risk individuals (P < 0.001). It showed moderate AUC (area under the curve) values for 1-, 2-, and 3-year overall survival prediction of 0.713 and could serve as an independent predictor for GC prognosis. Compared to the low-risk group, high-risk patients had higher expressions of marker genes for immune checkpoint inhibitors (ICIs) and showed higher sensitivity to the chemotherapy agents, rapamycin, bexarotene, and bicalutamide. Our findings demonstrate a robust prognostic model based on nine autophagy-related lncRNA pairs for GC. It acts as an independent predictor for survival and efficacy prediction of immunotherapy and chemotherapy in GC patients.