血清中肝细胞癌抑制因子1启动子高甲基化。一项针对乙型肝炎的诊断和预后研究。

Hepatocellular carcinoma suppressor 1 promoter hypermethylation in serum. A diagnostic and prognostic study in hepatitis B.

作者信息

Tian Ming-Ming, Fan Yu-Chen, Zhao Jing, Gao Shuai, Zhao Ze-Hua, Chen Long-Yan, Wang Kai

机构信息

Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.

Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China.

出版信息

Clin Res Hepatol Gastroenterol. 2017 Mar;41(2):171-180. doi: 10.1016/j.clinre.2016.10.003. Epub 2017 Feb 8.

DOI:10.1016/j.clinre.2016.10.003

PMID:28189396

Abstract

BACKGROUND

Liver cancer ranks as the second leading cause of cancer-related mortality in man worldwide, and hepatocellular carcinoma (HCC) is the most prevalent malignant neoplasm of the liver. The sensitivity of alpha-fetoprotein (AFP) as an HCC diagnostic marker for HCC diagnosis is 39-65%, and one-third patients with HCC are missed using AFP. New biomarkers are needed to diagnose HCC at an earlier stage and to individualize treatment strategies. Hepatocellular carcinoma suppressor 1 (HCCS1) is a newly identified liver tumor suppressor gene.

OBJECTIVE

Our study evaluated the diagnostic value of serum HCCS1 promoter methylation in patients with HCC associated with hepatitis B.

METHODS

We determined the methylation status of serum HCCS1 promoter in 120 patients with HCC, 146 patients with chronic hepatitis B (CHB) and 27 healthy controls (HCs) by methylation-specific polymerase chain reaction (MSP). Evaluation of a cohort with 63 patients with HCC and 44 patients with CHB was set as a validation dataset.

RESULTS

The frequency of HCCS1 promoter methylation in patients with HCC was significantly higher than that in patients with CHB (P<0.001) and HCs (P<0.001), and was associated with tumor node-metastasis (TNM) stage (P=0.01). The sensitivity of serum HCCS1 promoter methylation for discriminating patients with HCC from CHB was 62.5% and that of AFP alone was 55%. Notably, the sensitivity of serum HCCS1 promoter methylation plus AFP level was 81.7%.

CONCLUSION

HCCS1 has potential as a biomarker for diagnosis and prognosis of patients with HCC.

摘要

背景

肝癌是全球男性癌症相关死亡的第二大主要原因，肝细胞癌（HCC）是肝脏中最常见的恶性肿瘤。甲胎蛋白（AFP）作为HCC诊断标志物用于HCC诊断的敏感性为39%-65%，三分之一的HCC患者会被AFP漏诊。需要新的生物标志物来更早地诊断HCC并使治疗策略个体化。肝细胞癌抑制因子1（HCCS1）是一个新发现的肝脏肿瘤抑制基因。

目的

我们的研究评估了血清HCCS1启动子甲基化在乙型肝炎相关HCC患者中的诊断价值。

方法

我们采用甲基化特异性聚合酶链反应（MSP）测定了120例HCC患者、146例慢性乙型肝炎（CHB）患者和27例健康对照（HC）血清HCCS1启动子的甲基化状态。将一个包含63例HCC患者和44例CHB患者的队列评估作为验证数据集。

结果

HCC患者中HCCS1启动子甲基化频率显著高于CHB患者（P<0.001）和HC（P<0.001），且与肿瘤淋巴结转移（TNM）分期相关（P=0.01）。血清HCCS1启动子甲基化鉴别HCC与CHB患者的敏感性为62.5%，单独AFP的敏感性为55%。值得注意的是，血清HCCS1启动子甲基化加AFP水平的敏感性为81.7%。