DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study
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...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6354 |
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| author | Inês Faleiro Vânia Palma Roberto Secil Demirkol Canli Nicolas A. Fraunhoffer Juan Iovanna Ali Osmay Gure Wolfgang Link Pedro Castelo-Branco |
| author_facet | Inês Faleiro Vânia Palma Roberto Secil Demirkol Canli Nicolas A. Fraunhoffer Juan Iovanna Ali Osmay Gure Wolfgang Link Pedro Castelo-Branco |
| author_sort | Inês Faleiro |
| collection | DOAJ |
| description | 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 (<i>n</i> = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (<i>n</i> = 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. <i>ITGA4</i>, <i>SFN</i>, <i>ITGA2</i>, and <i>PIK3R1</i> methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of <i>SFN</i> and <i>PIK3R1</i> 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. |
| first_indexed | 2024-03-10T04:31:45Z |
| format | Article |
| id | doaj.art-5c371e0b76d74c418214320ca09c6e9d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:31:45Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5c371e0b76d74c418214320ca09c6e9d2023-11-23T04:07:35ZengMDPI AGCancers2072-66942021-12-011324635410.3390/cancers13246354DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based StudyInês Faleiro0Vânia Palma Roberto1Secil Demirkol Canli2Nicolas A. Fraunhoffer3Juan Iovanna4Ali Osmay Gure5Wolfgang Link6Pedro Castelo-Branco7Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, PortugalFaculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, PortugalMolecular Pathology Application and Research Center, Hacettepe University, 06100 Ankara, TurkeyCentre 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, FranceCentre 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, FranceDepartment of Medical Biology, Acibadem University, 34684 Istanbul, TurkeyInstituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, SpainFaculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, PortugalPancreatic 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 (<i>n</i> = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (<i>n</i> = 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. <i>ITGA4</i>, <i>SFN</i>, <i>ITGA2</i>, and <i>PIK3R1</i> methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of <i>SFN</i> and <i>PIK3R1</i> 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.https://www.mdpi.com/2072-6694/13/24/6354pancreatic cancerepigeneticsDNA methylationPI3K/AKT pathway |
| spellingShingle | Inês Faleiro Vânia Palma Roberto Secil Demirkol Canli Nicolas A. Fraunhoffer Juan Iovanna Ali Osmay Gure Wolfgang Link Pedro Castelo-Branco DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study Cancers pancreatic cancer epigenetics DNA methylation PI3K/AKT pathway |
| title | DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study |
| title_full | DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study |
| title_fullStr | DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study |
| title_full_unstemmed | DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study |
| title_short | DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study |
| title_sort | dna methylation of pi3k akt pathway related genes predicts outcome in patients with pancreatic cancer a comprehensive bioinformatics based study |
| topic | pancreatic cancer epigenetics DNA methylation PI3K/AKT pathway |
| url | https://www.mdpi.com/2072-6694/13/24/6354 |
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