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

HCC is the most prevalent gastrointestinal malignant tumor worldwide. Genetic determinants of HCC occurrence have been always an interest for most hepatologists. The aim of this research to discover if TLR2 gene (rs3804099) polymorphism and MicroRNA301 gene expression can affect HCC incidence in Egyptians. 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 participantswere subjected to clinical evaluation and history-taking, laboratory investigations and molecular testing (TLR2 SNP analysis and microRNA301 gene expression by qPCR). Results: Our study found that HCC patients were mainly males(60%),age was 53.67 +/- 7.62 years. TLR2 (rs3804099) CT, CC genotypes were significantly prominent in HCC patients (37.6% and 45.6%), CT prevails inhepatitis C patients (48.8%), and CT was the main genotype of healthy controls. Significant difference regarding genotypes (P=0.007) between HCC, control and (P=0.004) regarding (CT+CC) vs TT. Individuals carrying genotype CT were significantly associated with decreased risk of HCC (OR 1.95% CI, P= 0.204), 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 stages (P <0.001) and TNM classification with increased level in advanced stages, increased tumor size mainly with CC genotype [T4=27 (84.4%), T3 =5 (15.6%)]. We concluded that TLR2 SNP CC and CT variants carry the highest risk of HCC development, while microRNA301 expression can be considered diagnostic and prognostic marker in HCC Egyptian patients.