Dong Zhao-Ru, Zhang Chi, Cai Jia-Bin, Zhang Peng-Fei, Shi Guo-Ming, Gao Dong-Mei, Sun Hui-Chuan, Qiu Shuang-Jian, Zhou Jian, Ke Ai-Wu, Fan Jia
Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Tumour Biol. 2015 Apr;36(4):2763-71. doi: 10.1007/s13277-014-2900-2. Epub 2014 Dec 6.
The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.
5-羟甲基胞嘧啶（5-hmC）的缺失已被确定为几种恶性肿瘤的表观遗传特征。然而，其在肝内胆管癌（ICC）中的作用仍不清楚。我们的研究旨在探讨5-hmC水平在ICC诊断和预后预测中的作用。采用斑点印迹法、组织芯片技术和免疫组化方法检测5-hmC水平，并分析5-hmC水平与ICC临床病理参数之间的相关性。与配对的肝组织相比，大多数ICC组织呈现5-hmC缺失。此外，肝硬化和低分化组织亚组的5-hmC水平最低。我们发现，5-hmC水平未升高的ICC患者与淋巴结转移和TNM分期显著相关，而与血管侵犯、性别、年龄、乙肝病毒感染、肝硬化或分化程度无关。TNM分期高（III期和IV期）且有淋巴结转移的ICC患者的5-hmC水平显著低于TNM分期低（I期和II期）且无淋巴结转移的患者。进一步分析表明，低5-hmC水平与较差的总生存期（OS）和无病生存期（DFS）显著相关。重要的是，多因素分析表明，5-hmC水平、肿瘤直径、淋巴转移和肿瘤分化可作为ICC的独立预后因素。5-hmC的缺失与ICC的进展有关。我们的结果有助于提高ICC患者的诊断能力和术后监测水平。
