Androgen deprivation modulates gene expression profile along prostate cancer progression.
Hum Pathol
; 56: 81-8, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27342909
ABSTRACT
Androgen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Adenocarcinoma
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Antineoplásicos Hormonais
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Terapia Neoadjuvante
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Transcriptoma
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Antagonistas de Androgênios
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hum Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article