Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Lung Adenocarcinoma

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Hypoxia is a crucial microenvironmental factor in lung adenocarcinoma (LUAD). However, the prognostic value based on hypoxia and immune in LUAD remains to be further clarified. The hypoxia-related genes (HRGs) and immune-related genes (IRGs) were downloaded from the public database. The RNA-seq expression and matched complete clinical data for LUAD were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to model construction. Hypoxia expression profiles, immune cell infiltration, functional enrichment analysis, Tumor Immune Dysfunction and Exclusion (TIDE) score and the somatic mutation status were analyzed and compared based on the model. Moreover, immunofluorescence (IF) staining in human LUAD cases to explore the expression of hypoxia marker and immune checkpoint. A prognostic model of 9 genes was established, which can divide patients into two subgroups. There were obvious differences in hypoxia and immune characteristics in the two groups, the group with high-risk score value showed significantly high expression of hypoxia genes and programmed death ligand-1 (PD-L1), and maybe more sensitive to immunotherapy. Patients in the high-risk group had shorter overall survival (OS). This model has a good predictive value for the prognosis of LUAD. We constructed a new HRGs and IRGs model for prognostic prediction of LUAD. This model may benefit future immunotherapy for LUAD.

Identification of hypoxia‐related gene signatures based on multi‐omics analysis in lung adenocarcinoma

“… 41 Until now, several hypoxia‐related gene features have been built to predict survival rate of certain tumour types, such as ovarian cancer, 42 renal clear cell carcinoma, 43 hepatocellular carcinoma, 44 breast cancer, 45 melanoma 46 and prostate cancer. 47 Although the role of hypoxia‐related genes in prognosis prediction of LUAD has received extensive attention in recent years, 48 , 49 , 50 , 51 the role of hypoxia in LUAD was not fully elucidated. Several studies have combined hypoxia and immunization to predict the prognosis of patients with LUAD, and the constructed models also have good predictive performances.…”