Combination of potential biomarkers for diagnosis, prognosis and monitoring of hepatocellular carcinoma: liquid biopsy in the detection of mutations in driver genes and serum markers

• Grant number: 23/16586-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: João Renato Rebello Pinho
• Grantee: João Renato Rebello Pinho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Claudia Pinto Marques Souza de Oliveira ; Denise Cerqueira Paranagua Vezozzo ; Flavio Ferraz de Paes e Alcantara ; Leonardo Gomes da Fonseca ; Luiz Augusto Carneiro D'Albuquerque ; Michele Soares Gomes Gouvêa ; Roberta Verciano Pereira Yokogawa ; Venancio Avancini Ferreira Alves

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and lethal tumors worldwide. HCC management depends on reliable biomarkers for screening, diagnosing and monitoring the disease, as well as predicting response to therapy. Ultrasound has been the established standard technique in the diagnosis and follow-up of HCC. However, imaging techniques have their limitations, especially early in the disease. Therefore, there is an urgent need for reliable and minimally invasive biomarkers. Up to this date, alpha-fetoprotein (AFP) is the only serum biomarker used in clinical practice for the management of HCC. Nevertheless, AFP has low specificity and sensitivity. Another important point is that liver biopsy is not a routinely adopted procedure in international guidelines for monitoring patients with HCC as it is already for neoplasms in other tissues. Thus, liquid biopsies as a source of biomarkers have become the focus of clinical research. At HCFMUSP-ICESP, there is a great deal of knowledge accumulated in the follow-up of patients with hepatocellular carcinoma (HCC). The clinical-surgical staff provides care to these patients using the best medical knowledge available in the SUS, with a history of publications and accomplishments in various clinical, surgical and diagnostic specialties. In addition, the Department of Pathology has great expertise in validating molecular methods and their implementation for clinical use throughout the hospital complex. Therefore, there is an excellent opportunity to combine these experiences to evaluate groups of patients at different stages of the molecular evolution of carcinogenesis, with controlled and recorded follow-up. The overall objective of our project is to provide SUS with liquid biopsy methods for detecting mutations associated earlier with the development of HCC, as well as other biomarkers (GAAD and glypican-3) in populations at risk and in patients with relapse. Thus, different groups of patients were defined to assess the impact of using the technology, from screening individuals at increased risk of HCC, passing through patients with curative treatment, either by surgical resection or by transplants. We have selected the most frequent molecular alterations in the pathogenesis of HCC, from the TCGA and COSMIC databases, which will be evaluated by dPCR, in plasma and tissue samples, when available. In the end, we intend to identify these early mutations in risk groups and, in relapse. In these same samples, serological dosages will be performed with two commercial kits: GAAD and glypican-3. Combinations with different biomarkers are expected to open new perspectives for diagnosis, treatment and monitoring of HCC. (AU)