Circulating biomarkers in liquid biopsy for differential diagnosis between diabetes mellitus secondary to pancreatic ductal adenocarcinoma and type 2 diabetes

• Grant number: 22/10682-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2023
• Effective date (End): March 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Lucia Cardillo Corrêa Giannella
• Grantee: Luiz Henrique Gomes Matheus
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pancreatic ductal adenocarcinoma (PDCA) is a neoplasm with dismal prognosis usually diagnosed at advanced stages, when surgery is not a therapeutic option. New-onset diabetes mellitus (DM) is a paraneoplastic manifestation of PDAC and constitutes a window of opportunity for its early diagnosis, since it appears between 24 and 36 months before the diagnosis of the tumor in 80% of the patients. The clinical suspicion that a new-onset DM is not a type 2 DM (T2D), but a DM secondary to PDAC, has important clinical implications, as it may allow the diagnosis of the tumor at a resectable stage, increasing the chances of cure. In a previous study, (1) we validated the differential expression of three serum microRNAs (miRs) that had been identified in a Chinese cohort as capable of differentiating DM secondary to PDCA from T2D, and (2) we identified two mRNAs upregulated in extracellular vesicles (EVs) from the first group in comparison to the second. The present project aims to identify and validate new potential markers that may allow the diagnosis of PDAC in individuals with new-onset DM, based on the following analyzes (1) plasmatic concentrations of trefoil factor 2 (TFF2), (2) mass spectrometry and miR expression in plasma, (3) EVs isolated from serum, (4) EVs isolated from saliva. These variables will be used in different machine learning models, in an attempt to find an accurate diagnostic strategy. For these purposes, we will further evaluate plasma from participants of the study previously conducted (n=42 in the PDAC group; n=33 in the T2D group and n=30 controls) and we will collect samples from more individuals with PDAC for validation in an independent series.