RESUMO
In order to screen for differentially expressed genes that might be useful in diagnosis or therapy of prostate cancer we have used a custom made Affymetrix GeneChip containing 3950 cDNA fragments. Expression profiles were obtained from 42 matched pairs of mRNAs isolated from microdissected malignant and benign prostate tissues. Applying three different bioinformatic approaches to define differential gene expression, we found 277 differentially expressed genes, of which 98 were identified by all three methods. Fourteen per cent of these genes were not found in other expression studies, which were based on bulk tissue. Resultant candidate genes were further validated by quantitative RT-PCR, mRNA in situ hybridization and immunohistochemistry. AGR2 was over-expressed in 89% of prostate carcinomas, but did not have prognostic significance. Immunohistologically detected over-expression of MEMD and CD24 was identified in 86% and 38.5% of prostate carcinomas respectively, and both were predictive of PSA relapse. Combined marker analysis using MEMD and CD24 expression proved to be an independent prognostic factor (RR = 4.7, p = 0.006) in a Cox regression model, and was also superior to conventional markers. This combination of molecular markers thus appears to allow improved prediction of patient prognosis, but should be validated in larger studies.
Assuntos
Molécula de Adesão de Leucócito Ativado/metabolismo , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica , Glicoproteínas de Membrana/metabolismo , Neoplasias da Próstata/metabolismo , Molécula de Adesão de Leucócito Ativado/genética , Antígenos CD/genética , Biomarcadores Tumorais/genética , Antígeno CD24 , Análise por Conglomerados , Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/genética , Microdissecção , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Neoplásico/genética , Análise de SobrevidaRESUMO
BACKGROUND: The prognostic impact of tumor grading and staging is markedly reduced in organ confined or moderately differentiated prostate cancer, which underscores the importance of new prognostic markers. Evaluating public expression data of prostate cancer, we found an upregulation of the candidate gene CD24. METHODS: We examined immunohistochemically the expression of CD24 protein in 31 nodal metastases and 102 adenocarcinomas of the prostate and correlated our findings to clinicopathological parameters. RESULTS: CD24 expression was found in 48% of primary prostate cancer cases and in 68% of lymph node metastases. Kaplan Meier curves and Cox regression analysis showed that CD24 expression was strongly linked to significantly earlier disease progression (relative risk = 3.2), which was especially pronounced in organ confined, or moderately differentiated primary prostate tumors. CONCLUSIONS: We conclude that CD24 is an important prognostic tissue marker for prostate cancer which could help to define patients of low or high risk of recurrence.
