Expression patterns of candidate susceptibility genes HNF1ß and CtBP2 in prostate cancer: association with tumor progression.
Urol Oncol
; 32(4): 426-32, 2014 May.
Article
en En
| MEDLINE
| ID: mdl-24332637
ABSTRACT
OBJECTIVES:
Genome-wide association studies have identified variants at multiple loci associated with prostate cancer (PCa) risk. Some of these loci include candidate susceptibility genes, such as MSMB, HNF1ß, and C-terminal-binding protein (CtBP2). Except for MSMB, the clinicopathological significance of these genes has not been investigated. We therefore aimed to analyze their expression in PCa tissues, in relation with tumor progression and aggressiveness. METHODS AND MATERIALS Protein expression was evaluated by immunohistochemistry on tissue microarrays containing samples from normal prostate (NL, n = 91), high-grade prostatic intraepithelial neoplasia (PIN, n = 61), clinically localized PCa (CLC, n = 434), PCa metastases (M, n = 28), and castration-resistant PCa (CRC, n = 49). Moreover, mRNA expression for each marker was assessed by quantitative real-time polymerase chain reaction, on 53 frozen samples of NL, CLC, and CRC.RESULTS:
These genes were differentially expressed at the different stages of PCa natural history. MSMB expression decreased with disease development and progression. In contrast, nuclear HNF1ß and CtBP2 staining significantly increased in the CRC and M groups when compared with CLC, together with the transcripts levels. In patients with CLC, HNF1ß and CtBP2 nuclear expressions were strongly associated with cancer cell proliferation. After adjusting for the Gleason score and the pathological stage, none of the candidate genes was significantly predictive of recurrence after radical prostatectomy. In patients with CRC, CtBP2 nuclear staining was associated with shorter overall survival.CONCLUSIONS:
The decrease of MSMB expression during tumor progression strongly supports its role as a tumor-suppressor gene. Although its functions remain to be clarified in PCa cells, HNF1ß and CtBP2 are associated with cancer cell proliferation, tumor progression, and castration-resistant disease.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Biomarcadores de Tumor
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Neoplasia Intraepitelial Prostática
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Oxidorreductasas de Alcohol
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Factor Nuclear 1-beta del Hepatocito
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Neoplasias de la Próstata Resistentes a la Castración
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Recurrencia Local de Neoplasia
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Proteínas del Tejido Nervioso
Tipo de estudio:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Urol Oncol
Asunto de la revista:
NEOPLASIAS
/
UROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Francia