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Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

2015Journal article Open access
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dc.contributor.authorPires-Luís, Ana Sílvia
dc.contributor.authorVieira-Coimbra, Marcia
dc.contributor.authorQuintela Vieira, Ana Filipa
dc.contributor.authorCosta-Pinheiro, Pedro
dc.contributor.authorSilva-Santos, Rui
dc.contributor.authorDias, Paula C
dc.contributor.authorAntunes, Luís
dc.contributor.authorLobo, Francisco
dc.contributor.authorOliveira, Jorge
dc.contributor.authorGonçalves, Céline S
dc.contributor.authorCosta, Bruno M
dc.contributor.authorHenrique, Rui
dc.contributor.authorJerónimo, Carmen
dc.date.accessioned2019-06-28T15:50:51Z
dc.date.available2019-06-28T15:50:51Z
dc.date.issued2015
dc.description.abstractRenal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of 3 genes--SMYD2, SETD3, and NO66--was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity [area under curve (AUC) = 0.959], and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC = 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPires-Luís, A. S., Vieira-Coimbra, M., Vieira, F. Q., Costa-Pinheiro, P., Silva-Santos, R., Dias, P. C., Antunes, L., Lobo, F., Oliveira, J., Gonçalves, C. S., Costa, B. M., Henrique, R., & Jerónimo, C. (2015). Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication. Epigenetics, 10(11), 1033–1043. https://doi.org/10.1080/15592294.2015.1103578
dc.identifier.doi10.1080/15592294.2015.1103578pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/14164
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor & Francispt_PT
dc.relationSFRH/SINTD/94217/201pt_PT
dc.relationSFRH/ BD/70564/2010pt_PT
dc.relation.publisherversionhttps://www.tandfonline.com/doi/full/10.1080/15592294.2015.1103578pt_PT
dc.subjectBiomarkers, Tumorpt_PT
dc.subjectCarcinoma, Renal Cellpt_PT
dc.subjectChromosomal Proteins, Non-Histonept_PT
dc.subjectDiagnosis, Differentialpt_PT
dc.subjectEarly Detection of Cancerpt_PT
dc.subjectGene Expression Regulation, Neoplasticpt_PT
dc.subjectHistone Demethylasespt_PT
dc.subjectHistone-Lysine N-Methyltransferasept_PT
dc.subjectKidney Neoplasmspt_PT
dc.subjectPrognosispt_PT
dc.subjectUp-Regulationpt_PT
dc.titleExpression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognosticationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1043pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1033pt_PT
oaire.citation.titleEpigeneticspt_PT
oaire.citation.volume10pt_PT
person.familyNameCoimbra
person.familyNameQuintela Vieira
person.givenNameMarcia
person.givenNameAna Filipa
person.identifier.orcid0000-0002-4632-4823
person.identifier.orcid0000-0003-0130-7664
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication2ec09312-f42e-4932-ba2f-55e941968b87
relation.isAuthorOfPublication47123d10-a0ed-47cc-a751-721489a13446
relation.isAuthorOfPublication.latestForDiscovery47123d10-a0ed-47cc-a751-721489a13446

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