Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Lung Adenocarcinoma

Abstract Background: Lung adenocarcinoma (LUAD) is the most common form of non-small-cell lung cancer (NSCLC). Hypoxia has been found in 50 – 60% of locally advanced solid tumors and shown to be associated with poor prognosis in a variety of tumors, including NSCLC. The study focused on the hypoxia associated molecular hallmarks in LUAD.Methods: 15 hypoxia related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on the data from The Cancer Genome Atlas(TCGA). Then, we investigate the immune status under different hypoxia status. Subsequently, we constructed prognostic models based on hypoxic-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNAs (ceRNAs) theory.Results: Two clusters (cluster1 and cluster2) were identified with different hypoxia status, cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4 + T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB were higher in cluster 1, which indicated immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated prognostic under different hypoxia clusters and its related mRNAs, lncRNAs were identified, then built a ceRNAs network.Conclusion: This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of gene signature and ceRNA theory.