Hepatocellular carcinoma (HCC) is one of the most frequent cancers in Egypt in which there is high prevalence of hepatitis C virus (HCV) infection. Matrix metalloproteinases (MMPs) are multifunctional proteins that assume an urgent part in cell development, differentiation, inflammation and angiogenesis. MMPs gene polymorphism might be included in development of HCV-related HCC. The study expected to explore relationship of MMP-1,3 & 9 genes polymorphisms with liver cirrhosis and HCC patients.
This study included 128 individuals who were enrolled from Menoufia University Hospital in the period between October 2015 and August 2016 classified into the following; Group I: included 48 patients with HCC on top of liver cirrhosis, they were 26 males and 22 females with mean age (58.60±5.29); Group II: 50 patients with liver cirrhosis, they were 26 males and 24 females with mean age (56.74±5.21); and Group III: 30 healthy subjects as controls, they were 15 males and 15 females with mean age (56.30 ±7.30). Diagnosis of HCC was done by their characteristic features in two imaging methods (abdominal US & triphasic CT). All subjects except controls were positive for serum HCV RNA. Liver functions tests, AFP & CHILD score were assessed. Genes polymorphisms were made by PCR-RFLP.
HCC patients had higher mutant G2G2 (35.4%) and G2 allele (62.5%) of MMP-1 gene than both cirrhotic (P < 0.05) and control groups (P < 0.001). For MMP-3 gene, additionally, HCC patients had the most noteworthy predominance of mutant 5A/5A (22.9%) and 5A allele (52.1%) than both cirrhotic (P < 0.05) and control groups (P < 0.001). The results of MMP-9 gene uncovered higher frequency of mutant TT genotype and T allele in both HCC (56.3% and 74%, respectively) and cirrhotic groups (10% and 35%, respectively) than in the control group. In HCC patients, we detected a significant correlation between heterozygote G1/G2 and G2/G2 of MMP-1 gene and homozygote TT of MMP-9 with higher CHILD score, tumor size and stage (P < 0.05). Moreover, MMP-3 5A/6A had higher CHILD score, portal vein thrombosis and advanced stage (P < 0.05) compared with other genotypes.
MMP-1, 3, 9 gene mutation may be embroiled in progression of liver cirrhosis and hazard relationship for HCC development.
Menoufia University
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All authors have declared no conflicts of interest.