Abstract

Background:Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients. Subjects and methods: Two hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR. Results:Combination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C]. Conclusion:Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.

Highlights

  • Hepatocellular carcinoma (HCC) is one of cancer causes of death all over the world (Gupta et al, 2019)

  • Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world

  • Portal vein thrombosis is more frequent in HCC more than LC group (p

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of cancer causes of death all over the world (Gupta et al, 2019). MMPs include a family of endopeptidases which has the capacity of extracellular matrix proteins degradation and remodeling. They have important roles for progression of invasion and metastasis of malignant solid tumors (Kessenbrock et al, 2010). MMP-11 is a member of MMPs family, known astromelysin-3, is one of stromelysin subgroup that belongs to MMP superfamily (Zhang et al, 2016) It has been associated with HCC and its expression controls miR-125a-regulated proliferation, epithelial–mesenchymal transition and metastasis of HCC (Geervliet and Bansal, 2020). Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Conclusion: Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression

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