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

2021-12-17Journal article Open access
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dc.contributor.authorFaleiro, Inês
dc.contributor.authorRoberto, Vania 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.accessioned2022-01-10T15:27:28Z
dc.date.available2022-01-10T15:27:28Z
dc.date.issued2021-12-17
dc.date.updated2021-12-23T15:07:13Z
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 (<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.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.identifierdoi: 10.3390/cancers13246354
dc.identifier.citationCancers 13 (24): 6354 (2021)pt_PT
dc.identifier.doi10.3390/cancers13246354pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.1/17462
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectPancreatic cancerpt_PT
dc.subjectEpigeneticspt_PT
dc.subjectDNA methylationpt_PT
dc.subjectPI3K/AKT pathwaypt_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.startPage6354pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStream5876
person.familyNameFaleiro
person.familyNameRoberto
person.familyNameCastelo-Branco
person.givenNameInês
person.givenNameVânia
person.givenNamePedro
person.identifier1230353
person.identifier.ciencia-idAD14-A2D0-3B41
person.identifier.ciencia-id681E-40B7-331F
person.identifier.ciencia-idE015-7F8F-5CA1
person.identifier.orcid0000-0001-5178-3090
person.identifier.orcid0000-0002-8134-4045
person.identifier.orcid0000-0002-3453-3978
person.identifier.scopus-author-id27467657800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublicationbb25b5ad-1769-42be-a7d3-8fe76215aa23
relation.isAuthorOfPublication.latestForDiscoveryc730a868-0e9f-43e4-a354-10130b30b764
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