Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Abstract

Background: A hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma.

Methods: Lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index.

Results: Four genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4⁺ T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients.

Conclusion: The hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.

Keywords: TCGA; hypoxia; lung adenocarcinoma; prognostic factor; signature.