Gene Expression and PPAR-¿ Polymorphism in Steatotic Disease Associated with Metabolic Dysfunction and the Relationship with Hepatocellular Carcinoma

• Grant number: 24/21515-3
• 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: Pedro Francisco Mateus Neto
• 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: Metabolic dysfunction-associated steatotic liver disease (MASLD), considered a metabolic syndrome, is characterized by the accumulation of fat in the form of triglycerides in the liver. It represents the main cause for the development of severe liver diseases, such as cirrhosis and hepatocellular carcinoma (HCC), due to the formation of the inflammatory microenvironment and fibrosis derived from chronic steatosis. Additionally, recent studies have associated genetic polymorphisms with the development of lipid metabolic dysfunctions preceding steatosis, as well as the relationship with the progression of carcinogenesis in HCC and the association with MASLD. Objective: To analyze the gene expression of PPAR-¿ (peroxisome proliferator-activated receptor gamma) in tissue from patients with MASLD with and without HCC and the association with the genetic polymorphism of PPAR-¿-rs3856806, as well as survival and anatomopathological characteristics (infiltrations: vascular, lymphatic and perineural; cellular differentiation). Patients and Methods: Ninety patients will be studied, regardless of age, sex and ethnic group, distributed as follows: 30 with HCC and MASLD, 30 with HCC, and 30 with MASLD (control group), with formalin-fixed paraffin-embedded (FFEP) liver tissue samples. DNA and RNA extraction will be performed from FFEP tissue for genotyping and analysis of PPAR-¿ expression, respectively, by real-time quantitative polymerase chain reaction (qPCR). Demographic data and anatomopathological characteristics will be obtained from electronic medical records. For statistical analysis, the chi-square (X2) or Fisher's test, ANOVA with Post-Hoc, Wilcoxon and Mann Whitney tests will be used. An alpha error of 5% will be accepted. (AU)