Combined signature of nine immune-related genes: a novel risk score for predicting prognosis in hepatocellular carcinoma

Am J Transl Res. 2020 Apr 15;12(4):1184-1202. eCollection 2020.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. There is an urgent need to identify diagnostic and prognostic biomarkers of HCC pathogenesis and progression. Accordingly, in this study, we analyzed differentially expressed immune-related genes (IRGs) from 329 patients with HCC from The Cancer Genome Atlas datasets. Functional analysis revealed that the IRGs had potential effects on tumor immune processes, such as inflammatory responses and growth factor activity. In the training group, we constructed a nine-IRG formula to predict prognosis in patients with HCC. To validate the protein and mRNA levels of these IRGs, we used the Human Protein Atlas database and quantitative PCR analysis and found that most protein expression levels matched the corresponding mRNA expression levels. Furthermore, we also validated the prognostic value of the new risk model in another independent cohort (n = 277) from a Gene Expression Omnibus dataset (GSE14520). Our data suggested that there was a significant association between our risk model and patient prognosis. Stratification analysis showed that the nine-IRG signature was significantly associated with overall survival in men. Finally, the signature was found to be correlated with various clinicopathological features. Intriguingly, the prognostic index based on the IRGs reflected infiltration by several types of immune cells. In summary, our data provided evidence that the nine-IRG signature could serve as an independent biomarker to predict prognosis in patients with HCC.

Keywords: Hepatocellular carcinoma; gene expression omnibus; immune-related genes; prognostic signature; risk score; the cancer genome atlas.