Expression of miR-145-3p associated with clinical and prognostic characteristics in Cholangiocarcinoma

• Grant number: 21/02964-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• 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

Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer, with increasing incidence worldwide. Admittedly, molecular events mediated by microRNAs (miRNAs) can interfere with carcinogenesis. In this context, miR-145-3p, in addition to being involved in inflammatory processes, also acts as a tumor suppressor, with an inhibitory effect on cell proliferation and cycle and, consequently, on tumor growth, apoptosis, and angiogenesis, as well as in the methylation of DNA. Thus, the advent of molecular biology may contribute to innovations in diagnosis and therapeutic approaches for this type of highly aggressive tumor. Objectives - To analyze the expression of miR-145-3p involved in oncogenesis in patients with CCA and its association with lifestyle, comorbidities, and survival, as well as its potential as a diagnostic and prognostic marker. Methodology - 65 patients with CCA and 30 individuals without clinical, biochemical, and histopathological signs of CCA, who underwent video-cholecystectomy surgery (control group) will be studied. The demographic, anthropometric, clinical, and biochemical profile, and lifestyle, of both groups, will be obtained in a questionnaire and electronic medical record. The total RNA will be extracted from a sample of tumor tissue embedded in paraffin and fresh tissue from the gallbladder (control group). The analysis of miR-145-3p expression will be performed by real-time reverse transcription-polymerase chain reaction (RT-qPCR). The data will be analyzed statistically, according to the characteristics of the variables. To determine the discriminatory potential of miR-145-3p expression in relation to the types of CCA, the Receiver Operation Characteristic (ROC) curve will be used. Survival analysis will be estimated using the Kaplan-Meier curve. The differences between the Survival Curves obtained, for the variables, will be analyzed by the log-rank test or Wilcoxon test. The significance level will be admitted for value P <0.05. (AU)