title: Prognostication of OCT4 isoform expression in prostate cancer.
abstract: Cancer stem cells (CSCs) refer to a subset of tumor cells that self-renew and affect tumor heterogeneity. This model has attracted considerable interest in recent years due to its implications in the prognosis and clinical management of cancer because CSCs mediate the occurrence, growth, and recurrence of tumors. OCT4 is central to embryonic stem cell self-renewal and differentiation into specific lineages and encodes two chief isoforms that are generated by alternative splicing--OCT4A and OCT4B. Their function in prostate cancer (PCa) is unknown. The prognostic function of OCT4 isoforms in PCa samples was examined by immunohistochemistry (IHC) and sensitivity and specificity of the antibodies used were evaluated by molecular biology techniques. Biochemical and pathological data and specimens from 193 patients with PCa were evaluated retrospectively. IHC, western blot, immunofluorescence, and automated image analysis were also performed. IHC was performed on a tissue microarray, and western blot and immunofluorescence were performed using the PCa cell line DU-145. IHC expression of OCT4 isoforms correlated with biochemical and pathological parameters, particularly biochemical recurrence-free survival (BCRFS). Patients with higher levels of OCT4B had lower Gleason scores and decreased likelihood of experiencing biochemical recurrence (BR). OCT4A(+) OCT4B(-) patients had the shortest BCRFS, and positivity for OCT4B expression was an independent prognostic factor for BCRFS in the multivariate analysis. We conclude that the expression of OCT4B is a strong marker of good prognosis, and its presence is associated with a decreased likelihood of BR. Thus, OCT4B might represent a powerful clinical prognostic biomarker for PCa patients.
authors: Department of Anatomic Pathology, A.C. Camargo Cancer Hospital, Rua Professor Antônio Prudente 211, Liberdade, Sao Paulo, SP, 01509-900, Brazil.
authors: Marina França
authors: MF
authors: de Resende
authors: Ludmilla Thomé Domingos
authors: LT
authors: Chinen
authors: Samantha
authors: S
authors: Vieira
authors: Juliano
authors: J
authors: Jampietro
authors: Francisco Paulo
authors: FP
authors: da Fonseca
authors: José
authors: J
authors: Vassallo
authors: Luciene Cristina
authors: LC
authors: Campos
authors: Gustavo Cardoso
authors: GC
authors: Guimarães
authors: Fernando Augusto
authors: FA
authors: Soares
authors: Rafael Malagoli
authors: RM
authors: Rocha
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020033:Protein Isoforms
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