Omic-based strategies for the investigation of biomarkers for early diagnosis of patients with progressive biliary diseases

• Grant number: 19/15040-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2019
• Effective date (End): March 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal researcher: Regina Vincenzi Oliveira
• Grantee: Juliana Magalhães de Oliveira
• Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 16/22215-7 - Impact of inspiratory muscle training and aging on metabolic maping and autonomic modulation at rest and on cardiovascular, respiratory and metabolic responses to exercise in healthy men, AP.TEM

Abstract

Progressive Familial Intrahepatic Cholestasis (PFIC) is an autosomal recessive hereditary disease that can affect the secretion, flow, or excretion of bile salts in the liver. This disease leads to increased hepatotoxicity due to high concentrations of bile salts in the liver and is responsible for the development of cirrhosis and liver failure. Most of the time, the progression of PFIC to a chronic phase is related to late diagnosis of the disease, mainly because it only can be diagnosed through liver biopsy, which is expensive, invasive and often a time-consuming procedure. Therefore, alternative methods for diagnosis through the use of blood, saliva or urine is highly attractive. Additionally, these biofluids are widely attainable through less invasive methods and with greater access to the population. Primary sclerosing cholangitis (CEP) and primary biliary cholangitis (CBP) are autoimmune cholestatic liver diseases, which can be triggered by genetic predisposition. Both CEP and CBP are characterized by inflammation of the intra- and/or extrahepatic bile ducts leading to their destruction due to the retention of bile salts in the liver, which also causes secondary damage to hepatocytes and fibrosis. Patients with CEP present a diagnosis associated with inflammatory bowel disease and are at higher risk of developing gastrointestinal cancer. Omic analysis (metabolomic, lipidomic and/or proteomic) help several factors: 1- to obtain new biomarkers for early diagnosis; 2- biochemical elucidation of the disease with the purpose of assisting in the selection of the best therapy and treatment, and 3- in the development of new drugs that are effective to avoid the progression of the disease to a chronic stage, which requires organ transplantation. In this project, the main goals are to apply omic-based strategies as new tools for the identification of new biomarkers associated with different types of progressive biliary diseases, as well as to evaluate the effectiveness of the use of ursodeoxycholic acid (UDCA) in the patients affected by such diseases. To this purpose, in this study untarget metabolomic will be explored using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS). The metabolomic results are expected to provide insights to evaluate the biochemical differences in urine, plasma, and saliva of patients and control groups. Moreover, based on the omics strategy, it is expected to find new biomarkers to effectively help the diagnosis of different types of cholestasis or cholangitis and to understand the drug action at the molecular level, which may help in further studies for the development of new drugs. (AU)