Department of Biochemistry, Faculty of Science, Port-Said University, Egypt.
Internal Medicine Department , Oncology Center, Faculty of Medicine, Mansoura University, Egypt.
Clin Res Hepatol Gastroenterol. 2023 May;47(5):102110. doi: 10.1016/j.clinre.2023.102110. Epub 2023 Mar 11.
Hepatocellular carcinoma originates from hepatocytes as a result of the effects of numerous genetic variations. Interferon-Induced Transmembrane protein 3 (IFITM3) is involved in the processes of cellular differentiation, apoptosis, cell adhesion, and immune cell regulation. Matrix Metalloproteinase-9 (MMP-9) are zinc dependent endopeptidases that cleave extracellular matrix contents and play an important role in the progression of cancer.
The study aimed to outline the key molecular biology progression in hepatocellular carcinoma and the relationship between hepatocellular cancer and genetic polymorphisms of IFITM3 and MMP-9.
In total 200 patients with hepatocellular carcinoma patients (n=100) and a control group with Hepatitis C virus (n=100) which collected randomly from the EL-Mansoura oncology center during the interval between June 2020 and October 2021. The expression of MMP-9 and the IFITM3 SNP was investigated. MMP-9 gene polymorphisms were estimated by using PCR-RFLP and IFITM3 gene was detected using DNA sequencing, ELISA was used to measure protein levels of MMP-9 and IFITM3.
The T allele of MMP-9 was more frequent among patients (n=121) than control subjects (n=71). The C allele of IFITM3 was more frequent among patients (n=112) than control subjects (n=83), polymorphisms of the genes linked to a high risk of disease development, patients of MMP-9 (TT genotype), odd ratio (OR) = 2.63, IFITM3 (CC genotype), OR= 2.43.
We found that the genetic polymorphisms of MMP-9 and IFITM3 are related to the occurrence and development of hepatocellular carcinoma. This study might be utilized in clinical diagnosis and therapy and to provide a baseline for prevention.
肝细胞癌源于肝细胞，是多种遗传变异作用的结果。干扰素诱导跨膜蛋白 3（IFITM3）参与细胞分化、凋亡、细胞黏附和免疫细胞调节等过程。基质金属蛋白酶-9（MMP-9）是锌依赖性内肽酶，可裂解细胞外基质成分，在癌症进展中发挥重要作用。
本研究旨在概述肝细胞癌的关键分子生物学进展，以及肝细胞癌与 IFITM3 和 MMP-9 遗传多态性的关系。
共纳入 200 例肝细胞癌患者（n=100）和 100 例丙型肝炎病毒对照组患者，于 2020 年 6 月至 2021 年 10 月期间在曼苏拉肿瘤中心随机收集。研究人员检测了 MMP-9 和 IFITM3 SNP 的表达情况。采用 PCR-RFLP 法检测 MMP-9 基因多态性，DNA 测序法检测 IFITM3 基因，酶联免疫吸附法（ELISA）检测 MMP-9 和 IFITM3 蛋白水平。
患者组（n=121）MMP-9 的 T 等位基因频率高于对照组（n=71），IFITM3 的 C 等位基因频率高于对照组（n=83）。MMP-9（TT 基因型）和 IFITM3（CC 基因型）患者的多态性与疾病发展风险增加相关，OR 值分别为 2.63 和 2.43。
我们发现 MMP-9 和 IFITM3 的遗传多态性与肝细胞癌的发生和发展有关。本研究可为临床诊断和治疗提供参考，并为预防提供基础。
