研究动态
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测量原发性肝细胞癌组织中主要高甲基化肿瘤抑制基因的差异表达。

Measuring the differential expression of the major hypermethylated tumor suppressor genes in tissues of primary hepatocellular carcinoma.

发表日期:2024 Sep
作者: Khalda Sayed Amr, Wafaa Mohamed Ezzat, Ahmed Ibrahim Saleh, Ahmed Heiba, Hend Amin, Refaat Refaat Kamel, Noha Eltaweel, Hoda Henery, Amr Omaia, Reham Ibrahim Siddik, Yasser Abdelghany Abdelazeem Elhosary
来源: Epigenetics & Chromatin

摘要:

肝癌发生是一个多因素过程,由遗传和表观遗传异常的整合导致基因表达和功能异常。用单一生物标志物很难表征 HCC。我们的研究旨在检测埃及 HCC 患者中作为调节因子的 8 个甲基化基因(SOCS1、APC、Gadd45b、CDKN1B、P15、PAX6、STAT1 和 MSH2)的表达。这项研究对 30 名 HCC 组织样本进行了研究。埃及患者与作为对照的非癌性邻近肝硬化组织进行比较。组织样本取自在萨赫勒教学医院(埃及开罗)接受活体肝移植 (LDLT) 或肝切除术的患者。使用特殊定制设计的 PCR 阵列来分析与 HCC 相关的选定甲基化基因的表达谱。与肝硬化组织相比,HCC 组织中 SOCS1、APC、Gadd45b、CDKN1B、P15、PAX6、STAT1 和 MSH2 的表达较低( p 值分别 = 0.015、0.081、0.004、0.027、0.211、0.015、0.025 和 0.0001)。 5 个基因(SOCS1、APC、GAdd45b、CDKN1B 和 MSH2)显示出可用作 HCC 诊断生物标志物的能力,其截止值具有高灵敏度和特异性:分别为 1.05、1.17、0.995、0.546 和 0.125。至于其他3个基因(P15、PAX6、STAT1),PAX6基因的敏感性最高,截止值为0.3364。甲胎蛋白 (AFP) 与 5 个研究基因(SOCS1、APC、Gadd45b、STAT1 和 MSH2)之间显示显着负相关。选定的高甲基化基因(SOCS1、APC、Gadd45b、CDKN1B、P15、PAX6、 HCC组织样本中的STAT1和MSH2低于癌旁组织。应进一步研究它们的作用,以解开 HCC 发病机制的谜团。版权所有 © 2024 The Authors。由爱思唯尔公司出版。保留所有权利。
Hepatocarcinogenesis is a multifactorial process that arises from a integration of genetic and epigenetic anomalies leading to abnormal gene expression and function. It is difficult to characterize HCC with a single biomarker. Our study aimed at detecting the expression of a panel of 8 methylated genes (SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2) as regulatory factors among Egyptian patients with HCC.This study was conducted on HCC tissue samples of 30 Egyptian patients in comparison with their non-cancerous adjacent cirrhotic tissue as a control. Tissue samples were obtained from patients who have undergone living donor liver transplantation (LDLT) or liver resection at El Sahel Teaching Hospital (Cairo, Egypt). A special Custom designed PCR Arrays was used to analyze the expression profiles of chosen methylated genes associated with HCC.Expression of SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2 were lower in the HCC tissue compared to the cirrhotic tissue (pvalue = 0.015, 0.081, 0.004, 0.027, 0.211, 0.015, 0.025 and 0.0001 respectively). 5 genes (SOCS1, APC, GAdd45b, CDKN1B, and MSH2) showed the ability to be used as diagnostic biomarkers for HCC with high sensitivity and specificity values at cut off values: 1.05, 1.17, 0.995, 0.546, and 0.125 respectively. As for the other 3 genes (P15, PAX6, STAT1), PAX6 gene has the highest sensitivity at a cut off value of 0.3364. A significant negative correlation was shown between alpha fetoprotein (AFP) and 5 of the studied genes (SOCS1, APC, Gadd45b, STAT1, and MSH2).Expression of the selected hypermethylated genes (SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2) in HCC tissue samples was lower than adjacent tissue. Their role should be further studied to solve the mystery that surrounds the pathogenesis of HCC.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.