Sun Gaofeng, Zhang Chen, Feng Min, Liu Wensheng, Xie Huifang, Qin Qin, Zhao E, Wan Li
School of Public Health, Xinjiang Medical University Department of Chronic and Non-communicable Diseases Control, City Center for Disease Control and Prevention The Fifth Affiliated Hospital of Xinjiang Medical University Department of Inspection, Affiliated Tumor Hospital of Xinjiang Medical University Urumqi Health and Family Commission, Urumqi, China.
Medicine (Baltimore). 2017 Oct;96(41):e8279. doi: 10.1097/MD.0000000000008279.
This study is to investigate the methylation status of multiple tumor suppressor 1 (p16), secreted glycoprotein 2 (SLIT2), scavenger receptor class A, member 5 putative (SCARA5), and human runt-related transcription factor 3 (Runx3) genes in the peripheral blood of hepatocellular carcinoma (HCC).This is a case-control study. The peripheral blood samples were collected from 25 HCC patients, 25 patients with high risk of HCC (defined as "internal control group"), and 25 healthy individuals (defined as "external control group"), respectively. Then the methylation status of p16, SLIT2, SCARA5, and Runx3 genes in the blood samples were analyzed by pyrosequencing. The relationship between the methylation and the clinical features of HCC patients were evaluated.The methylation levels in the 7 CpG loci of p16 gene in HCC patients were low and without statistically significant difference (P > .05) compared to the control groups. Although the methylation levels of CpG3 and CpG4 in SLIT2 gene loci were higher than those of the control groups, there was no statistically significant difference (P > .05). However, the methylation rate of CpG2 locus in SCARA5 gene in HCC patients was significantly higher (P < .05). And the methylation rates of CpG1, CpG2, CpG3, CpG4, CpG5, and CpG8 in Runx3 gene in HCC patients were significantly different to that of control groups (P < .05). We also have analyzed the correlations between the CpG islands methylation of Runx3 or SCARA5 genes and the age, gender, hepatitis B, liver cirrhosis, alpha fetal protein, or hepatitis B surface antigen (HBsAg) of the HCC patients, which all showed no significant correlations (P > .05).The methylation status of SCARA5 and Runx3 genes are abnormal in HCC patients, which may further be used as molecular markers for early auxiliary diagnosis of liver cancer.
本研究旨在调查肝细胞癌（HCC）患者外周血中多种肿瘤抑制因子1（p16）、分泌糖蛋白2（SLIT2）、清道夫受体A类成员5（SCARA5）和人类 runt 相关转录因子3（Runx3）基因的甲基化状态。这是一项病例对照研究。分别从25例HCC患者、25例HCC高危患者（定义为“内部对照组”）和25名健康个体（定义为“外部对照组”）采集外周血样本。然后通过焦磷酸测序分析血样中p16、SLIT2、SCARA5和Runx3基因的甲基化状态。评估甲基化与HCC患者临床特征之间的关系。与对照组相比，HCC患者p16基因7个CpG位点的甲基化水平较低，且无统计学显著差异（P>0.05）。虽然SLIT2基因位点的CpG3和CpG4甲基化水平高于对照组，但无统计学显著差异（P>0.05）。然而，HCC患者SCARA5基因CpG2位点的甲基化率显著更高（P<0.05）。HCC患者Runx3基因的CpG1、CpG2、CpG3、CpG4、CpG5和CpG8甲基化率与对照组有显著差异（P<0.05）。我们还分析了Runx3或SCARA5基因的CpG岛甲基化与HCC患者的年龄、性别、乙型肝炎、肝硬化、甲胎蛋白或乙型肝炎表面抗原（HBsAg）之间的相关性，均无显著相关性（P>0.05）。HCC患者中SCARA5和Runx3基因的甲基化状态异常，这可能进一步用作肝癌早期辅助诊断的分子标志物。
