Construction and Validation of a Novel Prognostic T-Cell Exhaustion-Related ceRNA Network in Lung Adenocarcinoma

Abstract

Background. T cell exhaustion (TEX) is a state of T cells that is characterized by poor function of effectors and increased expression of inhibitory signals. However, the heterogeneity and prognostic values of TEX in lung adenocarcinoma (LUAD) remain not fully understood. Methods. Based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) transcriptomic profiles, we screened differentially expressed lncRNAs, miRNAs, and mRNAs and identified differentially expressed TEXs. Univariate cox and LASSO regression analyses were performed to construct TEX-related prognostic signature and risk score and validated their expression using real-time PCR assay. We then investigated the potential mechanism, immune landscape, and antitumor therapy response in LUAD. Results. A total of 315 DE-lncRNAs, 161 DE-miRNAs, and 2589 DEGs were screened, and then 80 DE-TEXGs were identified in LUAD. Based on univariate cox and LASSO regression analyses, CCNA2 and SLC2A1 were identified as TEX-related prognostic signatures, and the risk score subsequently was calculated. LUAD patients were divided into high- and low-risk groups, and high-risk groups were involved in poor survival status, immunosuppression, and more sensitive to anti-CTLA4 therapy. Finally, a TEX-related ceRNA network was constructed and validated based on DE-lncRNAs, DE-miRNAs, and TEX-related prognostic signatures. Conclusion. We constructed the TEX-related prognostic signature and its relevant ceRNA network and discovered the molecular mechanism and prognostic values of TEX in LUAD.