Duan Jin-Ling, Nie Run-Cong, Xiang Zhi-Cheng, Chen Jie-Wei, Deng Min-Hua, Liang Hu, Wang Feng-Wei, Luo Rong-Zhen, Xie Dan, Cai Mu-Yan
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Department of Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
J Hepatocell Carcinoma. 2021 May 28;8:493-505. doi: 10.2147/JHC.S309451. eCollection 2021.
To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.
The expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.
Histone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63-0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24-3.08, = 0.004; HR: 1.95, 95% CI: 1.12-3.42, = 0.019; and HR: 1.97, 95% CI: 1.39-2.80, < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15-3.48, = 0.01).
Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.
评估小肝细胞癌（小肝癌）中整体组蛋白修饰情况，并确定其在预测复发方面的预后价值。
采用免疫组织化学方法评估335例乙肝相关小肝癌患者中整体组蛋白修饰的表达谱，包括H2AK5AC、H2BK20AC、H3K4me2、H3K9AC、H3K18AC、H4K12AC和H4R3me2。然后使用最小绝对收缩和选择算子Cox回归开发了两个组蛋白特征分类器。使用该分类器和独立危险因素构建列线图。通过受试者工作特征曲线评估分类器和列线图的性能。
肿瘤组织中的组蛋白修饰比相邻肝组织更明显。在肿瘤组织中，基于七种组蛋白特征构建的风险评分显示出令人满意的预测效率，在训练队列中2年生存率的AUC = 0.71（0.63 - 0.79）。高风险评分患者的无复发生存期比低风险评分患者短（训练、验证和总队列的HR分别为：1.96，95%CI：1.24 - 3.08，P = 0.004；HR：1.95，95%CI：1.12 - 3.42，P = 0.019；HR：1.97，95%CI：1.39 - 2.80，P < 0.001）。此外，使用组蛋白分类器构建的早期复发统计列线图的C指数 = 0.68。在非肿瘤性肝组织中，基于H3K4me2和H4R3me2的肝脏特征与晚期复发相关（HR：2.00，95%CI：1.15 - 3.48，P = 0.01）。
肿瘤组织和相邻肝组织中的整体组蛋白修饰分别是乙肝相关小肝癌患者早期和晚期复发的新预测指标。
