TLR2 Gene Polymorphism and MicroRNA 301 gene Expression Level as a Signature for Hepatocellular Carcinoma in Egyptian Patients

Document Type : Original Article

Authors

1 Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebeen El‑Koum, Menoufia Egypt

2 Depatment of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El‑Koum, Menoufia Egypt

3 Department of physiology, Medical college, Alazhr University for girls, Egypt

4 Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebeen El‑Koum, Egypt

5 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El‑Kom, Menoufia, Egypt

Abstract

HCC is the most prevalent gastrointestinal malignant tumour worldwide. Genetic determinants of HCC occurrence have been always an interest for most hepatologists. The aim of our research to discover link between TLR2 gene (rs3804099) polymorphism, MicroRNA 301 gene expression and HCC incidence in an Egyptian cohort. Methodology: 247 participants were divided to 3 groups. Group 1: 85 adult HCC patients on top of HCV. Group 2: 82 chronic HCV patients. They were followed up for one year. 80 supposedly healthy subjects who were matched in age and sex with patients (Group 3). All participants were subjected to clinical evaluation and history-taking, laboratory investigations and molecular testing (TLR2 SNP analysis and microRNA 301 gene expression by qPCR). Results: Our study found that HCC patients were mainly males (60%), aged 53.67 ± 7.62years. TLR2 (rs3804099) CC genotype was significantly prominent in HCC patients (37,6%), CT prevails in hepatitis C patients (47,8%), while TT was the main genotype of healthy controls. Individuals carrying genotype TT were significantly associated with decreased risk of HCC (OR 1, 95% CI, P = 0.0001), while those of CC showed a higher HCC risk (OR 3.048 95% CI (1.269 – 7.320), P = 0.013). A highly significant variation in MicroRNA301 level regarding Barcelona B, D stages (P <0.001) and TNM classification with increased serum level in advanced stages, increased tumour size mainly with CC genotype [T3=27 (84.4%) T4 =5 (15.6%), lymph nodes (N2) and metastasis (M1)]. We concluded that TLR2 SNP CC variant carries the highest risk of HCC development, while microRNA301 expression can be considered diagnostic and prognostic marker in HCC Egyptian patients.

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