A New Hypoxia-Related Prognostic Risk Score (HPRS) Model Was Developed to Indicate Prognosis and Response to Immunotherapy for Lung Adenocarcinoma.

Background: Hypoxia is a typical microenvironmental feature of most solid tumors, affecting a variety of physiological processes. We developed a hypoxia-related prognostic risk score (HPRS) model to reveal tumor microenvironment (TME) and predict prognosis of lung adenocarcinoma (LUAD). Methods: LUAD sample expression data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) Cox regression identified hypoxia-related genes (HRGs) to create HPRS. The prognostic value, genetic mutation and TME, and therapeutic response of distinct HPRS groups were analyzed. Univariate and multivariate Cox regression analysis identified independent factors associated with the prognosis of LUAD. A decision tree based on HPRS and clinicopathological variables was established using the classification system based on decision tree algorithm. A nomogram was constructed with important clinical features and HPRS by the RMS package. Results: A HPRS model with five HRGs was developed and verified in two separate cohorts of GEO. HPRS model divided patients with LUAD into two groups. High HPRS was related to high probability of genetic alterations. HPRS could predict the prognosis, TME, and sensitivity to immunotherapy/chemotherapy of LUAD. The decision tree defined four risk subgroups with significant OS differences. Nomogram with integrated HPRS and clinical features had acceptable accuracy in predicting LUAD prognosis. Conclusions: A HPRS model was developed to evaluate prognosis, genetic alterations, TME, and response to immunotherapy, which may provide theoretical reference for the study of molecular mechanism of hypoxia in LUAD.