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Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Zhuomao Mo, Ling Yu, Zhirui Cao, Hao Hu, Shaoju Luo, Shijun Zhang

2020Frontiers in Genetics89 citationsDOIOpen Access PDF

Abstract

Background: hypoxia microenvironment has been verified for the effect in initiation and progression of many cancers, but its certain value in prognosis of lung adenocarcinoma is still unclear. The purpose of this research is to establish the hypoxia-associated signature in lung adenocarcinoma and explore the potential relationship between hypoxia and lung adenocarcinoma. Methods: The cases of lung adenocarcinoma were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The included genes were selected by univariate Cox regression analysis and lasso Cox regression analysis, and the signature was evaluated by survival analysis and multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was used to investigate the potential mechanism between signature and immune cells. Moreover, the nomogram was constructed and evaluated by C-index. Results: Four genes (XPNPEP1, ANGPTL4, SLC2A1 and PFKP) were finally included for establishing the signature. The results showed that patients in high risk group showed worsen survival than those in low risk group. Besides, we found two types of immune cells (T cell CD4 memory activated and Macrophages M0) infiltrated significantly into high risk group. Finally, the nomogram involving established signature was constructed. And the signature was verified to be an independent prognostic factor for lung adenocarcinoma. Conclusion: The established hypoxia-associated signature could serve as the potential prognostic factor in lung adenocarcinoma and may promote the immunotherapy for patients.

Topics & Concepts

NomogramAdenocarcinomaGene signatureLung cancerHypoxia (environmental)OncologyImmune systemProportional hazards modelGeneBiologyMedicineInternal medicineCancer researchGene expressionCancerImmunologyGeneticsOrganic chemistryChemistryOxygenFerroptosis and cancer prognosisCancer, Hypoxia, and MetabolismCancer Immunotherapy and Biomarkers