Circulating microRNAs in cancers of the liver, pancreas and the biliary tree: identification of potential biomarkers and functional characterization

• Grant number: 16/03905-2
• Support type: Regular Research Grants
• Duration: November 01, 2017 - October 31, 2019
• Field of knowledge: Biological Sciences - Morphology
• Principal researcher: Patricia Pintor dos Reis
• Grantee: Patricia Pintor dos Reis
• Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Assoc. researchers: César Tadeu Spadella ; Giovanni Faria Silva ; Igor Jurisica ; Juan Carlos Llanos ; Luciana Schultz Amorim ; Maria Aparecida Marchesan Rodrigues Kobayasi ; Robson Francisco Carvalho ; Rogério Antonio de Oliveira ; Silvia Regina Rogatto ; Wan L. Lam

Abstract

Cancers of the liver, pancreas and the biliary tree, collectively known as HPB (hepato-pancreato-biliary cancers), are aggressive carcinomas and are among the tumors with high complexity regarding diagnosis, prognosis and treatment. HPB carcinomas are associated with high morbidity and mortality rates, with >800,000 deaths/year, worldwide. Considering that the liver, the biliary tree and the pancreas share common progenitor cells in initial stages of development, which persist until adult age, the search for common as well as specific biomarkers for each HPB subsite may lead to better understanding of tumorigenesis mechanisms. Since early disease diagnosis is essential for better patient survival, the identification of blood-based and tumor-related biomarkers will likely provide useful information on disease development, progression and impact on survival. Of note, the role of microRNAs in regulating important cellular processes since early development suggests their clinical applicability as robust biomarkers and potential therapeutic molecules. microRNAs may be optimal biomarkers, as they are highly stable even in formalin-fixed, paraffin embedded samples and are found in high concentrations in blood. Detection of microRNAs in plasma and serum has been shown to be useful for early diagnosis and to predict prognosis and treatment response of patients with cancer. Therefore, our aims are (1) to identify deregulated microRNA expression levels in tumor and plasma of patients with HPB cancers; (2) to identify deregulated expression levels of microRNA-target genes in HPB tumors; (3) to perform functional assays for microRNAs and target genes, to experimentally demonstrate, in vitro, their specific regulation in HPB cancer cells and their role in tumorigenesis. This study will thus shed light into the role of specific microRNAs in HPB oncogenesis, and may also contribute to future development of clinically applicable diagnostic, microRNA-based strategies for patients with HPB carcinomas. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FELIX, TAINARA F.; LOPEZ LAPA, RAINER M.; DE CARVALHO, MARCIO; BERTONI, NATALIA; TOKAR, TOMAS; OLIVEIRA, ROGERIO A.; RODRIGUES, MARIA A. M.; HASIMOTO, CLAUDIA N.; OLIVEIRA, WALMAR K.; PELAFSKY, LEONARDO; et al. MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. PLoS One, v. 14, n. 5, MAY 31 2019. (14/00367-4, 16/03905-2)