Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications.
Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications.
复制标题
具有整体组蛋白修饰的乙型肝炎病毒相关小肝细胞癌患者早期和晚期复发风险分层的预后模型
DOI：
10.2147/jhc.s309451
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发表时间：
2021
影响因子：
4.1
通讯作者：
Cai MY
中科院分区：
文献类型：
--
作者：
Duan JL;Nie RC;Xiang ZC;Chen JW;Deng MH;Liang H;Wang FW;Luo RZ;Xie D;Cai MY
背景与目的评估小肝细胞癌（small HCC）中整体组蛋白修饰的概况，并确定其在预测复发方面的预后价值。方法应用免疫组织化学方法检测335例HBV相关小肝癌患者的组蛋白修饰表达谱，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。利用分类器和独立危险因素建立了nomogram。用接收者工作特征曲线评价分类器和nomogram的性能。结果组蛋白修饰在肿瘤组织中较邻近肝组织明显。在肿瘤组织中，基于7组蛋白特征建立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短于低风险评分患者（HR: 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，分别为训练、验证和总队列）。此外，使用组蛋白分类器构建的早期复发统计nomogram C-index = 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）。结论：在hbv相关的小肝癌患者中，肿瘤和邻近肝组织的整体组蛋白修饰分别是早期和晚期复发的新预测因子。
Background and Aim To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence. Methods 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. Results 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, p = 0.004; HR: 1.95, 95% CI: 1.12–3.42, p = 0.019; and HR: 1.97, 95% CI: 1.39–2.80, p < 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, p = 0.01). Conclusion Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.