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

Background: 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 cl...

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Authors: Rodríguez Berriguete, Gonzalo, Ortega Núñez, Miguel Ángel|||0000-0003-2588-1708, Torrealba Abache, Norelia Rosa, Martínez Onsurbe, María del Pilar, Olmedilla Arregui, Gabriel, Paniagua Gómez-Álvarez, Ricardo, Guil Cid, Manuel Esteban, Fraile Laiz, Benito|||0000-0002-4847-055X, Royuela García, María del Mar|||0000-0003-1999-9849
Format: article
Publication Date:2015
Country:España
Institution:Universidad de Alcalá (UAH)
Repository:e_Buah Biblioteca Digital Universidad de Alcalá
Language:English
OAI Identifier:oai:ebuah.uah.es:10017/32720
Online Access:http://hdl.handle.net/10017/32720
https://dx.doi.org/10.1186/s12885-015-1839-z
Access Level:Open access
Keyword:Apoptosis
Caspases
Biochemical progression
Inhibitors of apoptosis proteins
Prostate cancer
Aged
Biomarkers, Tumor
Caspase 3
Cohort Studies
Disease Progression
Follow-Up Studies
Humans
Inhibitor of Apoptosis Proteins
Male
Middle Aged
Predictive Value of Tests
Prognosis
Prostatectomy
Prostatic Neoplasms
X-Linked Inhibitor of Apoptosis Protein
Biología
Genética
Ciencia
Biology
Genetics
Science
Description
Summary:Background: 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. Methods: 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. Results: 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. Conclusions: 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.