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.

摘要

大约80%的原发性肝癌（PLC）为肝细胞癌（HCC），HCC患者预后不良。需要进一步的研究来开发新的预后工具来预测 HCC 患者的预后。单变量 Cox 和 LASSO 回归用于开发多基因风险评分。采用单样本基因集富集分析（ssGSEA）来评估免疫功能和细胞的差异。通过校准曲线和受试者工作特征曲线（ROC）评估模型性能。qRT-PCR用于评估临床样本中的基因表达。最后，开发了一种新的五基因（KIF20A、CENPA、HMMR、G6PD 和 ADH4）风险评分。根据患者风险评分的中值，将患者分为两组：高危组和低危组。高危组患者的总生存期（OS）明显低于低危组。五基因风险评分是与患者OS相关的独立危险因素。此外，还建立了由TNM分期和风险评分组成的列线图。决策曲线、校准曲线和ROC的结果表明，预后风险评分和列线图具有很好的预测能力。此外，HCC组织中ADH4的mRNA减少，而HCC组织中KIF20A、CENPA、HMMR和G6PD的mRNA过度表达。我们开发了一种新的五基因风险评分，可以预测 HCC 患者的预后。这五个基因可能是HCC的有希望的治疗靶点。五基因风险评分和列线图可能是 HCC 有用的预后工具。