Wu Junling, Lin Zeman, Ji Daihan, Li Zhenli, Zhang Huarong, Lu Shuting, Wang Shenglin, Liu Xiaolong, Ao Lu
Fujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350025, China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China.
Cancers (Basel). 2022 Aug 16;14(16):3957. doi: 10.3390/cancers14163957.
Recurrence is the main factor affecting the prognosis of early hepatocellular carcinoma (HCC), which is not accurately evaluated by clinical indicators. The metabolic heterogeneity of HCC hints at the possibility of constructing a stratification model to predict the clinical outcome. On the basis of the relative expression orderings of 2939 metabolism-related genes, an individualized signature with 10 metabolism-related gene pairs (10-GPS) was developed from 250 early HCC samples in the discovery datasets, which stratified HCC patients into the high- and low-risk subgroups with significantly different survival rates. The 10-GPS was validated in 311 public transcriptomic samples from two independent validation datasets. A nomogram that included the 10-GPS, age, gender, and stage was constructed for eventual clinical evaluation. The low-risk group was characterized by lower proliferation, higher metabolism, increased activated immune microenvironment, and lower TIDE scores, suggesting a better response to immunotherapy. The high-risk group displayed hypomethylation, higher copy number alterations, mutations, and more overexpression of immune-checkpoint genes, which might jointly lead to poor outcomes. The prognostic accuracy of the 10-GPS was further validated in 47 institutional transcriptomic samples and 101 public proteomic samples. In conclusion, the 10-GPS is a robust predictor of the clinical outcome for early HCC patients and could help evaluate prognosis and characterize molecular heterogeneity.
复发是影响早期肝细胞癌（HCC）预后的主要因素，而临床指标无法准确评估复发情况。HCC的代谢异质性提示构建分层模型以预测临床结局的可能性。基于2939个代谢相关基因的相对表达排序，从发现数据集中的250例早期HCC样本中开发了一个包含10个代谢相关基因对（10-GPS）的个体化特征，该特征将HCC患者分为高风险和低风险亚组，两组生存率差异显著。10-GPS在来自两个独立验证数据集的311个公共转录组样本中得到验证。构建了一个包含10-GPS、年龄、性别和分期的列线图用于最终的临床评估。低风险组的特征是增殖较低、代谢较高、免疫微环境激活增加以及TIDE评分较低，提示对免疫治疗反应较好。高风险组表现为低甲基化、较高的拷贝数改变、突变以及免疫检查点基因更多的过表达，这些可能共同导致不良结局。10-GPS的预后准确性在47个机构转录组样本和101个公共蛋白质组样本中进一步得到验证。总之，10-GPS是早期HCC患者临床结局的可靠预测指标，有助于评估预后并表征分子异质性。
