Identification and Validation of Hypoxia-Related lncRNA Signature as a Prognostic Model for Hepatocellular Carcinoma

Front Genet. 2021 Sep 28;12:744113. doi: 10.3389/fgene.2021.744113. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC) is one of the most general malignant tumors. Hypoxia is a critical clinical characteristic and acts as a significant part in the development and cancers' prognosis. The prognostic value and biological functions of hypoxia-related lncRNAs in hepatocellular carcinoma is little known. Thus, we aim to establish a hypoxia-related lncRNA signature to predict the HCC patients' survival. First, we extracted the hypoxia-related genes and expression of lncRNAs from the MSigDB and TCGA database, respectively. The co-expression analysis among hypoxia-related mRNAs and lncRNAs was employed to identify hypoxia-related lncRNAs. Then, comprehensive analyses of lncRNAs expression level and survival data were applied to establish the signature. We built a prognostic signature on the foundation of the three differently expressed hypoxia-related lncRNAs. Kaplan-Meier curves indicated the low-risk group is associated with better survival. The 1-, 3-, and 5 years AUC values of the signature were 0.805, 0.672 and 0.63 respectively. The test set performed consistent outcomes. A nomogram was built grounded on the risk score and clinicopathological features. GSEA showed the immune-related pathways in high-risk group, while metabolism-related pathways in low-risk group. Besides, we found this model was correlated with the clinical features, tumor immune cell infiltration, immune checkpoints, and m6A-related genes. Finally, a novel signature based on hypoxia-related lncRNAs was established and validated for predicting HCC patients' survival and may offer some useful information for immunotherapies.

Keywords: hepatocellular carcinoma; hypoxia; immune cells infiltration; immune checkpoint; lncRNA; m6A; prognosis.