Biomarkers of Carcinogenesis in Differential Anatomopathological Diagnosis in Bileopancreatic Malignant Neoplasms

• Grant number: 22/01832-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2022
• End date: February 29, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Dorotéia Rossi Silva Souza
• Grantee: Pedro Henrique Fogaça Jordão
• 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

Abstract

Introduction: Biliopancreatic malignant neoplasms are the second leading cause of death from cancer of the digestive tract, after colorectal cancer. Among the main types of cancer of the biliopancreatic system, cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (ACDP) stand out, whose anatomopathological similarities make it difficult or impossible to differentiate between the primary origin of these diseases. To date, there are no molecular markers to differentiate ACDP from CCA. In this context, the joint analysis of molecular markers that participate in carcinogenic pathways such as tumor promoters and suppressors, angiogenesis and apoptosis, may contribute to the differentiation of these malignant neoplasms. Objectives: To analyze the gene expression of SMAD4, TGF-²1, VEGF-A, HIF-1±, PIK3CA and PTEN in patients with ACDP and CCA, as well as the respective proteins, in order to identify potential differential diagnostic markers for these diseases. Methods: 74 individuals will be studied: 30 patients with CCA, 30 patients with ACDP and 14 controls, being 7 samples of cystic duct from patients with cholelithiasis and 7 samples of pancreatic tissue from necropsy, all without clinical, biochemical and histopathological signs of the aforementioned neoplasms. RNA will be extracted from paraffin tissue samples for gene expression analysis. In addition, immunohistochemical analysis of the respective markers will be performed in the tumor tissues and in the control group. Clinical data will be obtained from electronic medical records. For statistical analysis, the following tests will be used: chi-square (Ç2), Wilcoxon, Mann Whitney and Receiver Operating Characteristic (ROC), considering areas under the curve e0.7 as clinically relevant. An alpha error of 5% will be allowed.