Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients’ prognosis

Journal of Hematology & Oncology

Tarek A Bismar¹  Bryan Donnelly⁴  Michael Dolph²  Samar A Hegazy²  Mohammed Alshalalfa¹  Samir Al Bashir³ 

[1] The Prostate Cancer Center, Calgary, AB, Canada;Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada;Department of Pathology and Laboratory Medicine, Jordan University of Science and Technology, Irbid, Jordan;Department of Urology, University of Calgary, Calgary, AB, Canada

关键词: Molecular subtypes;    Poorest outcome;    Prostate cancer;    Biological pathways;    PTEN;    ERG;    CRISP3;   

Others  :  801754
DOI  :  10.1186/1756-8722-7-21

 received in 2014-01-16, accepted in 2014-03-03,  发布年份 2014

【 摘 要 】

Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for prognostic validation. Results showed, CRISP3 protein intensity to be significantly associated with neoplastic epithelium, being highest in CRPC vs. benign prostate tissue (p < 0.0001), but was not related to Gleason score (GS). CRISP3 mRNA was significantly associated with higher GS (p = 0.022 in MSKCC, p = 1.1e-4 in Swedish). Significant association between CRISP3 expression and clinical outcome was documented at the mRNA but not the protein expression levels. CRISP3 mRNA expression was related to biochemical recurrence in the MSKCC (p = 0.038) and lethal disease in the Swedish cohort (p = 0.0086) and retained its prognostic value in the subgroup of patients with GS 6 & 7. Furthermore, CRISP3 protein and mRNA expression was significantly associated with positive ERG status and with PTEN deletions. Functional biology analysis documented phenylalanine metabolism as the most significant pathway governing high CRISP3 and ERG expression in this subtype of PCA. In conclusion, the combined status of CRISP3, ERG and PTEN define a molecular subtype of PCA with poorest and lethal outcome. Assessing their combined value may be of added value in stratifying patients into different prognostic groups and identify those with poorest clinical outcome.

【 授权许可】

   
2014 Al Bashir et al.; licensee BioMed Central Ltd.

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