Characterization of Long Non-Coding RNAs Associated with the Cancer Stem Cell Phenotype in Pancreatic Ductal Adenocarcinoma.

• Grant number: 24/21592-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Daniela Sanchez Basseres
• Grantee: Nicolas Paulino Rezende
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pancreatic ductal adenocarcinoma (PDAC), which accounts for over 90% of pancreatic neoplasms, is a highly lethal cancer with a 5-year survival rate below 10%. This is largely due to aggressive metastatic dissemination. A critical factor for metastasis is the tumor stem cell phenotype, mediated by cancer stem cells (CSCs), which are responsible for tumor maintenance, chemoresistance, and metastasis. However, the molecular mechanisms underlying the CSC phenotype in pancreatic CSCs remain poorly understood, limiting therapeutic advances. Since this process is predominantly epigenetic, we hypothesize that long non-coding RNAs (lncRNAs) play a key role. Using public RNAseq data from PDAC patients (The Cancer Genome Atlas, TCGA), we calculated the mRNA stemness index (mRNAsi) and identified lncRNAs differentially expressed in patients with high and low stemness indices. This project aims to: (1) validate the differential expression of lncRNAs in PDAC CSC models in vitro; (2) assess the prognostic value of these lncRNAs using data from the International Cancer Genome Consortium (ICGC) and TCGA; and (3) explore their enrichment in pancreatic tumors compared to adjacent normal tissue using bulk and single-cell RNAseq data. We aim to validate lncRNAs with prognostic potential in PDAC CSCs, providing a foundation for their functional study and potential development as therapeutic targets. (AU)