Validation of lncRNA as risk biomarkers for hepatocellular carcinoma in advanced Hepatitis C

• Grant number: 21/04753-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Adriana Camargo Ferrasi
• Grantee: Adriana Camargo Ferrasi
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Geysson Javier Fernandez Garcia ; Giovanni Faria Silva ; Maria Inês de Moura Campos Pardini

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Surgical resection and liver transplantation are the main treatment options, however, the results are limited, and the prognosis is poor, mainly due to late diagnosis. Nonspecific or absent symptoms in HCC require monitoring of individuals at high risk using ultrasound and alpha-fetoprotein (AFP) dosage, looking for early diagnosis. Environmental and genetic factors are involved in hepatic carcinogenesis and approximately 80% of cases are associated with hepatitis B or C. Despite advances in the diagnosis and treatment of hepatitis C, which effectively reduce the risk of developing HCC, these resources are not yet available to most patients and this cancer represents a public health problem in Brazil. An increasing number of long non-coding RNAs (lncRNAs) have already been associated with the genesis and progression of cancer. Studies have demonstrated the role of lncRNA with oncogenic or tumor suppressor activities, suggesting a great potential in the treatment, diagnosis or indicator of prognosis in cancer. Recently, our research group in collaboration with researchers in Portugal and Colombia identified, using next-generation sequencing (NGS), 37 lncRNAs differentially expressed in hepatitis C and hepatocellular carcinoma, some of them potential biomarkers of specific stages of the disease. Among them, some have already been classified as tumor suppressors in HCC or other tumors, however, most of them are unpublished and without functional description. Such markers are of clinical interest both in prognosis and as therapeutic targets. In this context, the purpose of the present study will be to validate, by Real-Time PCR, at least ten of the lncRNAs identified with differential expression and evaluate them as potential biomarkers of the high risk for HCC in plasma of patients with advanced hepatitis C. The identification of biomarkers of high risk for the disease could make possible, in the medium term, the development of an early diagnostic method, the only real chance of survival of a patient affected by this type of cancer. This project will have the contribution of Prof. Dr. Geysson Javier Fernandez Garcia of the University of Antioquia (Colombia), consolidating the scientific collaboration between the two universities. (AU)