Derivation of a Novel CIHI in Patients with Lung Adenocarcinoma for Estimating Tumor Microenvironment and Clinical Prognosis

Abstract

An interaction between hypoxia and immunity has been confirmed in tumor tissue. However, there is no combined biomarker for diagnosis on this basis. Therefore, we developed a scoring formula based on markers of hypoxia and immunity. Firstly, the hypoxia-immune formula of lung adenocarcinoma (LUAD) was derived using LASSO-Cox regression in three cohorts from public database, and the corresponding score was calculated for each patient. The formula is as follows: $\text{combined}\text{hypoxia}\text{and}\text{immune}\text{index}\left(\text{CIHI}\right)=\text{LDHA}\text{expression}\times 0.2252+\text{GAPDH}\text{expression}\times 0.0727+\text{ANGPTL}4\text{expression}\times 0.0724+\text{VEGFC}\text{expression}\times 0.1911+\text{DKK}1\text{expression}\times 0.1355+\text{ADM}\text{expression}\times 0.0588+\text{BTK}\text{expression}\times -0.1659$ . Meanwhile, patients were divided into groups according to high and low CIHI, and expression profiles of hypoxia markers and immune markers were analyzed in different groups. CIHI was used to confirm that patients with high CIHI represented a state of hypoxiahigh-immunitylow, which had worse overall survival. We also discussed the evaluation value in the immune microenvironment and clinical application of CIHI. In conclusion, this study developed and validated a hypoxia-immune formula that can guide hypoxia modifier treatment and immunotherapy in LUAD.