Identification of Hypoxia-Related Prognostic Signature and Competing Endogenous RNA Regulatory Axes in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common type of liver cancer and one of the highly lethal diseases worldwide. Hypoxia plays an important role in the development and prognosis of HCC. This study aimed to construct a new hypoxia-related prognosis signature and investigate its potential ceRNA axes in HCC. RNA profiles and hypoxia genes were downloaded, respectively, from the Cancer Genome Atlas hepatocellular carcinoma database and Gene Set Enrichment Analysis website. Cox regression analyses were performed to select the prognostic genes and construct the risk model. The ENCORI database was applied to build the lncRNA-miRNA–mRNA prognosis-related network. The TIMER and CellMiner databases were employed to analyze the association of gene expression in ceRNA with immune infiltration and drug sensitivity, respectively. Finally, the co-expression analysis was carried out to construct the potential lncRNA/miRNA/mRNA regulatory axes. We obtained a prognostic signature including eight hypoxia genes (ENO2, KDELR3, PFKP, SLC2A1, PGF, PPFIA4, SAP30, and TKTL1) and further established a hypoxia-related prognostic ceRNA network including 17 lncRNAs, six miRNAs, and seven mRNAs for hepatocellular carcinoma. Then, the analysis of immune infiltration and drug sensitivity showed that gene expression in the ceRNA network was significantly correlated with the infiltration abundance of multiple immune cells, the expression level of immune checkpoints, and drug sensitivity. Finally, we identified three ceRNA regulatory axes (SNHG1/miR-101-3p/PPFIA4, SNHG1/miR-101-3p/SAP30, and SNHG1/miR-101-3p/TKTL1) associated with the progression of HCC under hypoxia. Here, we constructed a prognosis gene signature and a ceRNA network related to hypoxia for hepatocellular carcinoma. Among the ceRNA network, six highly expressed lncRNAs (AC005540.1, AC012146.1, AC073529.1, AC090772.3, AC138150.2, AL390728.6) and one highly expressed mRNA (PPFIA4) were the potential biomarkers of hepatocellular carcinoma which we firstly reported. The three predicted hypoxia-related regulatory axes may play a vital role in the progression of hepatocellular carcinoma.