Identification of a new five-gene risk score for risk stratification and prognosis prediction in HCC.

ABSTRACT

Approximately 80% of primary liver cancer (PLC) is hepatocellular carcinoma (HCC), and the prognosis of HCC patients is unfavorable. Further studies are required to develop new prognostic tools for predicting the HCC patients' prognosis. The univariate Cox and LASSO regression were utilized to develop the multi-gene risk score. Single-sample Gene Set Enrichment Analysis (ssGSEA) was employed to assess differences of immune functions and cells. The model performance was evaluated by calibration curve and receiver operating characteristic curve (ROC). And qRT-PCR was utilized to evaluate the genes expression in clinical samples. Finally, a novel five-gene (KIF20A, CENPA, HMMR, G6PD, and ADH4) risk score was developed. Based on the median value of patients' risk scores, patients were divided into two groups high-risk group and low-risk group. The Overall survival (OS) of patients in high-risk group was obviously poorer than that in the low-risk group. And the five-gene risk score was an independent risk factor correlated with patients' OS. Besides, a nomogram consisting of TNM stage and risk score was established. The results of decision curve, calibration curve, and ROC presented that the prognostic risk score and the nomogram had great predictive capability. Besides, ADH4's mRNA was reduced in HCC tissues, while the mRNA of KIF20A, CENPA, HMMR, and G6PD were overexpressed in HCC tissues. We developed a novel five-gene risk score that could predict HCC patients' prognosis. And these five genes could be promising therapeutic targets for HCC. The five-gene risk score and nomogram may be useful prognostic tools for HCC.