Impact of miRNA-221-3p Expression on Inflammatory Pathways in Hepatic and Biliary-Pancreatic Malignant Neoplasms

• Grant number: 25/01850-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Dorotéia Rossi Silva Souza
• Grantee: Maria Eduarda Menezes Pedrozo
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
• Associated research grant: 23/01068-0 - Differential Biomarkers for the Anatomopathological Diagnosis of Malignant Biliopancreatic Neoplasms, AP.R

Abstract

Introduction: Malignant neoplasms of the hepatic and biliopancreatic systems, represented by hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and pancreatic ductal adenocarcinoma (PDAC), compromise the functionality of the liver, bile ducts, and pancreas, accounting for the third leading cause of cancer-related deaths worldwide. The decisive role of the inflammatory process in tumorigenesis is emphasized, from initiation to more advanced stages such as malignant transformation, invasion, and metastasis. Chronic inflammation can create a favorable environment for cancer development and progression, including hepatic, biliary, and pancreatic neoplasms. In this context, evidence has pointed to the relationship of microRNAs, such as miR-221-3p, in modulating the expression of genes involved in inflammatory pathways. Studying this interaction is essential to understand how altered miR-221-3p expression can influence the tumor microenvironment in the aforementioned neoplasms, as these conditions are often associated with chronic inflammations such as viral hepatitis, cirrhosis, cholecystitis, and pancreatitis.Objectives: To analyze the expression of miRNA-221-3p in hepatic and biliopancreatic neoplasms and its association with the histopathological profile, identifying target genes of this microRNA related to inflammation in PDAC, HCC, and CCA, using bioinformatics tools.Case Series and Methods: 150 individuals will be studied, distributed into four groups: Study Group I - 40 patients with CCA; Study Group II - 40 patients with PDAC; Study Group III - 40 patients with HCC; Control Group I (intrahepatic duct and common bile duct); Control Group II (pancreatic duct); Control Group III (hepatic parenchyma) - 10 individuals in each group, subjected to necropsy, all without clinical, biochemical, or histopathological signs of the referred neoplasms. Clinical data and lifestyle habits will be obtained from electronic medical records. Tumor tissue samples and control groups, fixed in formalin and embedded in paraffin, will undergo RNA extraction for miRNA-221-3p expression analysis by quantitative real-time polymerase chain reaction (RT-qPCR). Data will be analyzed statistically, with a significance level set for P<0.05.