Song ZeBing, Zhang GuoPei, Yu Yang, Li ShaoQiang
Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Genet. 2021 Aug 23;12:689801. doi: 10.3389/fgene.2021.689801. eCollection 2021.
Dysregulation of autophagy-related genes (ARGs) is related to the prognosis of cancers. However, the aberrant expression of ARGs signature in the prognosis of hepatocellular carcinoma (HCC) remain unclear. Using The Cancer Genome Atlas and the International Cancer Genome Consortium database, 188 common autophagy-related gene pairs (ARGPs) were identified. Through univariate, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis, a prognostic signature of the training set was constructed on the basis of 6 ARGPs. Further analysis revealed that the ARGP based signature performed more accurately in overall survival (OS) prediction compared to other published gene signatures. In addition, a high risk of HCC was closely related to CTLA4 upregulation, LC3 downregulation, low-response to axitinib, rapamycin, temsirolimus, docetaxel, metformin, and high-response to bleomycin. Univariate Cox and multivariate Cox analysis revealed that the risk score was an independent prognostic factor for HCC. These results were internally validated in the test and TCGA sets and externally validated in the ICGC set. A nomogram, consisting of the risk score and the TNM stage, performed well when compared to an ideal nomogram. In conclusion, a 6-ARGP-based prognostic signature was identified and validated as an effective predictor of OS of patients with HCC. Furthermore, we recognized six small-molecule drugs, which may be potentially effective in treating HCC.
自噬相关基因（ARGs）的失调与癌症的预后相关。然而，ARGs特征在肝细胞癌（HCC）预后中的异常表达仍不清楚。利用癌症基因组图谱和国际癌症基因组联盟数据库，鉴定出188对常见的自噬相关基因对（ARGPs）。通过单变量、最小绝对收缩和选择算子分析以及多变量Cox回归分析，基于6对ARGPs构建了训练集的预后特征。进一步分析表明，与其他已发表的基因特征相比，基于ARGP的特征在总生存期（OS）预测中表现更准确。此外，HCC的高风险与CTLA4上调、LC3下调、对阿西替尼、雷帕霉素、替西罗莫司、多西他赛、二甲双胍的低反应以及对博来霉素的高反应密切相关。单变量Cox分析和多变量Cox分析表明，风险评分是HCC的独立预后因素。这些结果在测试集和TCGA集中进行了内部验证，并在ICGC集中进行了外部验证。与理想的列线图相比，由风险评分和TNM分期组成的列线图表现良好。总之，基于6对ARGP的预后特征被鉴定并验证为HCC患者OS的有效预测指标。此外，我们识别出六种小分子药物，它们可能对治疗HCC有潜在疗效。
