Hagag Neven A, Ali Yasser B M, Elsharawy Ahmed A, Talaat Roba M
Clinical Pathology Department, National Live Institute (NLI), Menufyia University, Sheben-Elkom, Egypt.
Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, Egypt.
J Gastrointest Cancer. 2020 Mar;51(1):234-241. doi: 10.1007/s12029-019-00234-9.
Liver cirrhosis (LC) is considered to be the end stage of chronic hepatopathies which may lead to hepatocellular carcinoma (HCC). Glypican-3 is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may participate in cancer development and progression. In this study, we aimed to evaluate the relation between the expression of miR-1291 and GPC3 production as a non-invasive tool to differentiate patients with LC and HCC.
HCV patients (100) were divided into two groups; HCC (I) and LC (II). Fifty hepatitis-free subjects served as the control group (III). Expression of serum GPC3 was performed by enzyme-linked immunosorbent assay, and expression of circulating miR-1291 was performed by quantitative real-time polymerase chain reaction (qRT-PCR).
Serum levels of GPC3 were significantly elevated in patients with HCC compared with the LC group. Both groups have increased GPC3 levels in relation to healthy controls. Serum GPC3 levels with a cutoff value of 619.5 pg/ml had a 50% sensitivity and 89.3% specificity while alpha-fetoprotein (AFP) with a cutoff value of 8.5 ng/ml had a higher sensitivity (87.5%) and specificity (100%) in the detection of HCC. The primary use of both markers improved the specificity to 100%. miR-1291 was significantly upregulated in HCC and LC patients compared with control subjects.
Our findings might indicate that miR-1291 exert oncogenic effects in hepatic carcinogenesis through positive regulation of GPC3 expression. We propose that GPC3 overexpression and its associated oncogenic effects are linked to the upregulation of miR-1291 in HCV patients.
肝硬化（LC）被认为是慢性肝病的终末期，可能导致肝细胞癌（HCC）。磷脂酰肌醇蛋白聚糖-3是HCC最有前景的血清标志物之一。微小RNA（miRNA）的异常表达可能参与癌症的发生和发展。在本研究中，我们旨在评估miR-1291表达与GPC3产生之间的关系，作为一种区分LC和HCC患者的非侵入性工具。
将100例丙型肝炎病毒（HCV）患者分为两组；HCC组（I）和LC组（II）。50名无肝炎受试者作为对照组（III）。采用酶联免疫吸附测定法检测血清GPC3的表达，采用定量实时聚合酶链反应（qRT-PCR）检测循环miR-1291的表达。
与LC组相比，HCC患者的血清GPC3水平显著升高。与健康对照组相比，两组的GPC3水平均升高。血清GPC3水平的临界值为619.5 pg/ml时，敏感性为50%，特异性为89.3%，而甲胎蛋白（AFP）临界值为8.5 ng/ml时，在检测HCC方面具有更高的敏感性（87.5%）和特异性（100%）。两种标志物的联合使用可将特异性提高到100%。与对照组相比，HCC和LC患者的miR-1291显著上调。
我们的研究结果可能表明，miR-1291通过正向调节GPC3表达在肝癌发生中发挥致癌作用。我们提出，GPC3的过表达及其相关的致癌作用与HCV患者中miR-1291的上调有关。
