Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy.

The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers.

We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer - clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival - and evaluated its capability to predict biochemical progression after radical prostatectomy.

Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman's test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed.

cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage.

Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression.

BMC cancer. 2015 Oct 27*** epublish ***

Gonzalo Rodríguez-Berriguete, Norelia Torrealba, Miguel Angel Ortega, Pilar Martínez-Onsurbe, Gabriel Olmedilla, Ricardo Paniagua, Manuel Guil-Cid, Benito Fraile, Mar Royuela

Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. Department of Pathology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. Department of Pathology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. Department of Urology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. 

PubMed      Full Text Article

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