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Expression of EMT-related genes CAMK2N1 and WNT5A is increased in locally invasive and metastatic prostate cancer

2019-10-15Journal article Open access
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dc.contributor.authorCarneiro, Isa
dc.contributor.authorVieira, Filipa Quintela
dc.contributor.authorLobo, João
dc.contributor.authorMoreira-Barbosa, Catarina
dc.contributor.authorMenezes, Francisco Duarte
dc.contributor.authorMartins, Ana Teresa
dc.contributor.authorOliveira, Jorge
dc.contributor.authorSilva, Regina
dc.contributor.authorJerónimo, Carmen
dc.contributor.authorHenrique, Rui
dc.date.accessioned2021-11-05T15:50:25Z
dc.date.available2021-11-05T15:50:25Z
dc.date.issued2019-10-15
dc.description.abstractProstate cancer (PCa) varies clinically from very indolent, not requiring therapeutic intervention, to highly aggressive, entailing radical treatment. Currently, stratification of PCa aggressiveness is mostly based on Gleason score, serum PSA and TNM stage, but outcome prediction in an individual basis is suboptimal. Thus, perfecting pre-therapeutic discrimination between indolent and aggressive PCa, avoiding overtreatment is a major challenge. Epithelial to mesenchymal transition (EMT) allows epithelial cells to acquire mesenchymal properties, constituting a critical step in tumor invasion and metastization. Thus, we hypothesized that EMT-related markers might allow for improved assessment of PCa aggressiveness. Using RealTime ready Custom Panel 384 assay, 93 EMT-related genes were assessed in normal prostate tissues (NPT, n=5), stage pT2a+b-PCa (n=5) and stage pT3b-PCa (n=5), from which CAMK2N1, CD44, KRT14, TGFβ3 and WNT5A genes emerged as the most significantly altered. Expression levels were then evaluated in a larger series (16 NPT and 94 PCa) of frozen tissues using quantitative RT-PCR. Globally, CAMK2N1, CD44 and WNT5A displayed higher expression levels at higher stages and less differentiated PCa. CAMK2N1 and WNT5A immunoexpression analysis disclosed significantly lower expression in NPT and increasing proportion of high-expression cases from pT2a+b to pT3b and metastatic PCa. Furthermore, higher CAMK2N1 and WNT5A transcript levels associated with shorter disease-free and disease-specific survival. In multivariable analysis, a trend for WNT5A expression levels to independently predict DFS was disclosed (p=0.056). Globally, our findings suggest an association between PCa aggressiveness and increased expression of CAMK2N1 and WNT5A, reflecting the acquisition of effective EMT characteristics by PCa cells.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCarneiro, I., Quintela-Vieira, F., Lobo, J., Moreira-Barbosa, C., Menezes, F. D., Martins, A. T., Oliveira, J., Silva, R., Jerónimo, C., & Henrique, R. (2019). Expression of EMT-Related Genes CAMK2N1 and WNT5A is increased in Locally Invasive and Metastatic Prostate Cancer [Research Paper]. Journal of Cancer, 10(24), 5915-5925. https://doi.org/10.7150/jca.34564pt_PT
dc.identifier.doi10.7150/jca.34564pt_PT
dc.identifier.eissn1837-9664
dc.identifier.urihttp://hdl.handle.net/10400.22/18822
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPMCpt_PT
dc.relation.publisherversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856586/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectProstate cancerpt_PT
dc.subjectEpithelial-to-mesenchymal transitionpt_PT
dc.subjectPrognosispt_PT
dc.subjectCAMK2N1pt_PT
dc.subjectWNT5Apt_PT
dc.titleExpression of EMT-related genes CAMK2N1 and WNT5A is increased in locally invasive and metastatic prostate cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage5925pt_PT
oaire.citation.startPage5915pt_PT
oaire.citation.titleJournal of Cancerpt_PT
oaire.citation.volume10pt_PT
person.familyNameQuintela Vieira
person.familyNameSilva
person.givenNameAna Filipa
person.givenNameRegina
person.identifier.ciencia-id871B-D071-507D
person.identifier.orcid0000-0003-0130-7664
person.identifier.orcid0000-0002-8373-1217
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication47123d10-a0ed-47cc-a751-721489a13446
relation.isAuthorOfPublication60471846-7876-49e1-b405-6ffe770795ae
relation.isAuthorOfPublication.latestForDiscovery60471846-7876-49e1-b405-6ffe770795ae

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