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DNA methylation of PI3K/AKT pathway-related genes predicts outcome in patients with pancreatic cancer: a comprehensive bioinformatics-based study

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dc.contributor.authorFaleiro, Inês
dc.contributor.authorRoberto, Vânia Palma
dc.contributor.authorDemirkol Canli, Secil
dc.contributor.authorFraunhoffer, Nicolas A.
dc.contributor.authorIovanna, Juan
dc.contributor.authorGure, Ali Osmay
dc.contributor.authorLink, Wolfgang
dc.contributor.authorCastelo-Branco, Pedro
dc.date.accessioned2022-01-04T13:50:03Z
dc.date.available2022-01-04T13:50:03Z
dc.date.issued2021
dc.description© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractPancreatic 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.pt_PT
dc.description.sponsorshipThis work was supported by the FCT Research Center Grant UID/BIM/04773/2013 CBMR 1334, Câmara Municipal de Loulé, by the Liga Portuguesa Contra o Cancro/Portuguese League against Cancer through the Grant LPCC-PT Foundation 2016 to V.P.R. and by the Spanish Ministry of Science, Innovation and Universities through Grant RTI2018-094629-B-I00 to W.L.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancers (Basel). 2021 Dec 17;13(24):6354pt_PT
dc.identifier.doi10.3390/cancers13246354pt_PT
dc.identifier.eissn2072-6694
dc.identifier.urihttp://hdl.handle.net/10451/50687
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/journal/cancerspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDNA methylationpt_PT
dc.subjectPI3K/AKT pathwaypt_PT
dc.subjectEpigeneticspt_PT
dc.subjectPancreatic cancerpt_PT
dc.titleDNA methylation of PI3K/AKT pathway-related genes predicts outcome in patients with pancreatic cancer: a comprehensive bioinformatics-based studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.issue24pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication8279804a-bbf8-47ac-a5f5-d5137ba7cb27
relation.isProjectOfPublication.latestForDiscovery8279804a-bbf8-47ac-a5f5-d5137ba7cb27

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