Zhong Anjing, Tian Yiping, Zhang Honghe, Lai Maode
Department of Pathology and Pathophysiology, Cancer Research Center, School of Medicine, Hangzhou, Zhejiang University, Zhejiang, P. R. China.
Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, P. R. China.
J Surg Oncol. 2018 Apr;117(5):1029-1037. doi: 10.1002/jso.24978. Epub 2018 Mar 12.
A total of 71 cases of colorectal carcinoma with hepatic metastasis were enrolled from the Department of Pathology of SIR RUN RUN SHAW Hospital. Paired primary tumors, hepatic metastases, and normal mucosa samples were collected from formalin-fixed paraffin-embedded tissues by manual macrodissection. And global levels of DNA methylation and hydroxymethylation in these tissues, measured by an ELISA-like microplate-based colorimetric methods. The immunohistochemical expression of 5-methylcytosine and 5-hydroxymethylcytosine were analyzed also.
The levels of DNA methylation in both primary and metastatic tumors were elevated when compared with normal mucosa, while DNA hydroxymethylation decreased slightly in those tissues. Similar results were observed in immunohistochemical staining. DNA methylation in hepatic metastases differed significantly in lymph node metastases (P = 0.037). And DNA hydroxymethylation in colorectal primary carcinoma was significantly different between tumor grade group (P = 0.018) and gender group (P = 0.048) respectively. And survival analyzes revealed that higher levels DNA hydroxymethylation were associated with better prognosis in colorectal primary carcinoma (P < 0.05).
DNA hydroxymethylation correlated with less aggressive tumor behavior in colorectal cancer and were identified as an independent prognostic factor in patients' overall survival, and downregulation of DNA hydroxymethylation may serve as a useful biomarker for colorectal cancer prognosis evaluation.
从邵逸夫医院病理科纳入71例结直肠癌肝转移患者。通过手动宏观解剖从福尔马林固定石蜡包埋组织中收集配对的原发性肿瘤、肝转移灶和正常黏膜样本。采用基于酶联免疫吸附测定（ELISA）的微孔比色法测量这些组织中的DNA甲基化和羟甲基化总体水平。同时分析5-甲基胞嘧啶和5-羟甲基胞嘧啶的免疫组化表达情况。
与正常黏膜相比，原发性肿瘤和转移瘤中的DNA甲基化水平均升高，而这些组织中的DNA羟甲基化略有下降。免疫组化染色也观察到类似结果。肝转移灶中的DNA甲基化在淋巴结转移方面存在显著差异（P = 0.037）。结直肠癌原发性肿瘤中的DNA羟甲基化在肿瘤分级组（P = 0.018）和性别组（P = 0.048）之间分别存在显著差异。生存分析显示，结直肠癌原发性肿瘤中较高水平的DNA羟甲基化与较好的预后相关（P < 0.05）。
DNA羟甲基化与结直肠癌中侵袭性较低的肿瘤行为相关，并被确定为患者总生存的独立预后因素，DNA羟甲基化的下调可能作为结直肠癌预后评估的有用生物标志物。
