Relationship between interferon-induced transmembrane protein 3 and matrix metalloproteinase-9 gene polymorphisms in patients with hepatocellular carcinoma

Clin Res Hepatol Gastroenterol. 2023 May;47(5):102110. doi: 10.1016/j.clinre.2023.102110. Epub 2023 Mar 11.

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Gene polymorphisms; Hepatitis C virus; Hepatocellular carcinoma; Interferon-induced transmembrane protein-3; Matrix metalloproteinase-9.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Interferons
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Matrix Metalloproteinase 9* / genetics
  • Membrane Proteins / genetics
  • Polymorphism, Single Nucleotide
  • RNA-Binding Proteins* / genetics

Substances

  • IFITM3 protein, human
  • Interferons
  • Matrix Metalloproteinase 9
  • Membrane Proteins
  • RNA-Binding Proteins