RASSF1A 和 SOCS1 基因甲基化状态作为肝细胞癌的一种非侵入性标志物。

RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Cancer Biomark. 2019;24(2):241-247. doi: 10.3233/CBM-181638.

DOI:10.3233/CBM-181638

PMID:30689554

Abstract

BACKGROUND

DNA methylation status is one of the most prevalent molecular alterations in human cancers. Identification of powerful diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) without a biopsy is urgently required.

OBJECTIVE

The purpose of this study was to determine the methylation status of RASSF1A and SOCS-1genes as a non-invasive biomarker for HCC identification and prognosis.

METHODS

Methylation specific-PCR technique was performed to recognize the methylation status of RASSF1A and SOCS-1 genes in 100 patients with HCC, 100 patients with liver cirrhosis (LC) but without HCC were considered as cirrhotic liver control group and 100 healthy control.

RESULTS

Methylation of RASSF1A and SOCS-1 genes were detected in 40% and 38% of HCC patients respectively, 14% and 20% of LC patients respectively. Methylation of SOCS-1 gene in peripheral blood of healthy control was 23%. Methylation of RASSF1A gene was associated with age, tumor size, vascular invasion and α fetoprotein (AFP), while SOCS-1 gene methylation was significantly associated with tumor size and AFP. Furthermore, using RASSF1A/ SOCS-1/ AFP panel improve diagnostic sensitivity for HCC 86% and specificity of 75%.

CONCLUSION

RASSF1A and SOCS1 genes methylation status may play an important role in the process of hepatocarcinogenesis and may be used as diagnostic and prognostic noninvasive biomarkers for HCC when combined with serum AFP.

摘要

背景

DNA 甲基化状态是人类癌症中最常见的分子改变之一。迫切需要一种无需活检即可识别用于诊断和预测肝细胞癌（HCC）的强大诊断和预后生物标志物。

目的

本研究旨在确定 RASSF1A 和 SOCS-1 基因的甲基化状态作为 HCC 识别和预后的非侵入性生物标志物。

方法

采用甲基化特异性 PCR 技术检测 100 例 HCC 患者、100 例无 HCC 的肝硬化（LC）患者作为肝硬化肝脏对照组和 100 例健康对照组的 RASSF1A 和 SOCS-1 基因的甲基化状态。

结果

在 HCC 患者中，分别检测到 RASSF1A 和 SOCS-1 基因的甲基化分别为 40%和 38%，LC 患者分别为 14%和 20%。健康对照组外周血 SOCS-1 基因的甲基化率为 23%。RASSF1A 基因甲基化与年龄、肿瘤大小、血管侵犯和α胎蛋白（AFP）有关，而 SOCS-1 基因甲基化与肿瘤大小和 AFP 显著相关。此外，使用 RASSF1A/SOCS-1/AFP 联合panel 可将 HCC 的诊断敏感性提高到 86%，特异性提高到 75%。