DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study.

Autor: Faleiro I; Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal.; Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal.; Instituto de Medicina Molecular João Lobo Antunes (IMM), Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal., Roberto VP; Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal.; Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal.; Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal.; Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal., Demirkol Canli S; Molecular Pathology Application and Research Center, Hacettepe University, 06100 Ankara, Turkey., Fraunhoffer NA; Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France., Iovanna J; Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Institut Paoli-Calmettes, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France., Gure AO; Department of Medical Biology, Acibadem University, 34684 Istanbul, Turkey., Link W; Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain., Castelo-Branco P; Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal.; Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal.; Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Dec 17; Vol. 13 (24). Date of Electronic Publication: 2021 Dec 17.
DOI: 10.3390/cancers13246354
Abstrakt: Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database ( n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas ( n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4 , SFN , ITGA2 , and PIK3R1 methylation levels could be independent prognostic indicators of patients' survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients' clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.
Databáze: MEDLINE
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