Lu Chang-Yi, Chen Shih-Ya, Peng Hui-Ling, Kan Pu-Yeh, Chang Wan-Chi, Yen Chia-Jui
Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Oncotarget. 2017 Jan 24;8(4):6406-6418. doi: 10.18632/oncotarget.14115.
Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients.
肝细胞癌（HCC）是一种预后差、死亡率高的高度恶性肿瘤。目前缺乏有效的早期诊断工具，因此肝切除术和肝移植是仅有的有效治疗方法。检测HCC最常用的标志物是血清甲胎蛋白（AFP），其敏感性和特异性较低。由于基因和微小RNA（miRNA）的异常DNA甲基化在大多数癌症早期就会出现，我们探讨了循环甲基化标志物是否可能成为有前景的HCC诊断临床工具。我们采用全基因组方法，在HCC中鉴定出许多高甲基化的miRNA。此外，将三个异常甲基化的基因和一个miRNA组合起来建立了一个甲基化预测模型，并测试了其在HCC中的诊断和预后潜力。使用血浆样本，该预测模型对乙肝相关HCC表现出高敏感性和特异性（>80%）。最重要的是，该模型检测出了近75% AFP水平在20 ng/mL时无法确诊的患者。此外，该预测模型在预测HCC患者5年总生存率方面表现出极高的能力。这些数据证明了HCC患者血浆中甲基化标志物具有很高的诊断和预后潜力。
