title: Deregulated expression of selected histone methylases and demethylases in prostate carcinoma.
abstract: Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR. SMYD3, SUV39H2, PRMT6, KDM5A, and KDM6A were upregulated, whereas KMT2A-E (MLL1-5) and KDM4B were downregulated in PCa, compared with normal prostate tissues. Remarkably, PRMT6 was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly, EZH2 and SMYD3 expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably, SMYD3 expression levels were of independent prognostic value for the prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especially SMYD3, might be of clinical usefulness for the assessment of PCa patients and assist in pre-therapeutic decision-making.
authors.affiliation: Cancer Epigenetics Group, Portuguese Oncology Institute, Research Center, Rua Dr António Bernardino Almeida, 4200-072 Porto, Portugal School of Allied Health Sciences (ESTSP), Polytechnic of Porto, Portugal Department of Pathology Department of Epidemiology Department of Urology, Portuguese Oncology Institute, Porto, Portugal Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Filipa Quintela
authors.initials: FQ
authors.lastname: Vieira
authors.forename: Pedro
authors.initials: P
authors.lastname: Costa-Pinheiro
authors.forename: João
authors.initials: J
authors.lastname: Ramalho-Carvalho
authors.forename: Andreia
authors.initials: A
authors.lastname: Pereira
authors.forename: Francisco Duarte
authors.initials: FD
authors.lastname: Menezes
authors.forename: Luís
authors.initials: L
authors.lastname: Antunes
authors.forename: Isa
authors.initials: I
authors.lastname: Carneiro
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D012334:RNA, Neoplasm; D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: biomarker; microarray; molecular biology; neoplasia; prostate