A Risk-Assessing Signature Based on Hypoxia- and Immune-Related Genes for Prognosis of Lung Adenocarcinoma Patients

Abstract

Lung Adenocarcinoma (LUAD) drastically influences human health. Tumor hypoxia and immunity impact hugely on the immunotherapeutic effect of LUAD patients. This study is aimed at exploring the prognostic markers associated with hypoxia and immunity in LUAD patients and evaluates their reliability. The relationship between hypoxia and immune-related genes and prognoses of LUAD patients was investigated by the univariate regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were used to reveal the enriched pathways and biological processes of prognosis-related genes. Univariate, LASSO, and multivariate Cox regression analyses were used to construct a prognostic signature and verify its independence. The reliability of the signature was evaluated by the Principal Component Analysis (PCA), the Kaplan-Meier (K-M) curve, and the receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA), tumor mutational burden (TMB), and single-sample GSEA (ssGSEA) further verified the performance of the signature. Finally, a prognostic signature for LUAD was constructed based on 7 hypoxia- and immune-related genes. According to riskScores acquired from the signature, the test set was divided into groups, where the prognosis of high-risk patients was poor. The feature genes had good reliability, and the riskScore could be used as an independent prognostic factor for LUAD patients. Meanwhile, high TMB scores and low immune scores were found in high-risk patients, and feature genes were enriched in signaling pathways such as cell cycle and p53 signaling pathway. In sum, a prognostic signature based on 7 hypoxia- and immune-related genes was constructed.