Relationship of the expression of the NF1, p53, bcl-2, pRB proteins with DNA/RNA of viruses and mutations of the BRCA 1/2 and hMSH2 genes in liver cancer

Abstract

Among tumors of the gastrointestinal tract, the incidence and mortality from primary liver cancer remains high. Over the past 20 years, the incidence of liver cancer in Belarus has increased by 45.7 %. The aim of the study was to establish the relationship between the expression of the NF1, p53, bcl-2 proteins and the pRB genes with DNA/RNA of viruses and mutations of the BRCA 1/2 and hMSH2 genes in liver cancer. Patients (n = 303) with morphologically established primary liver cancer were examined. A molecular biological and immunological study was performed: antibodies to cell-cycle NF1, p53, bcl-2, pRB proteins, DNA/RNA of viruses, the BRCA 1/2, hMSH2 gene. The levels of antibodies to p53, bcl-2, pRB, and NF1 in the serum of healthy individuals differed from those in blood samples and tissue extracts from patients with hepatitis C, liver cancer and in native liver tissue samples. Mutations in liver cancer were (p = 0.004): in the tumor tissue – 6.13 %, in the blood – 0.85 %. Changes in the hMSH2 gene in the tissue were set at 15.48 %. DNA/RNA was isolated in the tumor tissue: HSV 1/2 – 56.1 %, HHV6 – 24.4, CMV – 17.1, HCV – 17.1, HBV – 4.9, HPV – 4.1, VEB – 2.4 %. Including mixed persistence – 26.8 %. In hepatitis (C, B) and liver cancer with CMV carriers, the expression of bcl-2, NF1 and pRb1 (p = 0.001) increases. The Epstein–Barr virus leads to the activity of the p53 protein in liver cancer (p = 0.003). The p53, bcl-2, pRB, and NF1 proteins in the liver tissue do not depend on the age and sex of patients. The degree of their influence on the function of genes with regard to DNA/RNA of viruses and mutations present in the genome (BRCA 1/2, hMSH2) suggests the degree of oncogenicity of viruses. The concentrations of p53, bcl-2, pRB, and NF1 in the blood, exceeding the predicted ones, for 50.8 year old persons, indicate the risk of development/presence of a tumor process in the liver.