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 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.
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. g.rodriguezb@uah.es.
Gonzalo
G
Rodríguez-Berriguete
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. engastediamante@gmail.com.
Norelia
N
Torrealba
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. miguel.angel.ortega92@gmail.com.
Miguel Angel
MA
Ortega
Department of Pathology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. mmonsurbe@salud.madrid.org.
Pilar
P
Martínez-Onsurbe
Department of Pathology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. golmedilla.hupa@salud.madrid.org.
Gabriel
G
Olmedilla
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. Ricardo.paniagua@uah.es.
Ricardo
R
Paniagua
Department of Urology, Príncipe de Asturias Hospital, 28805, Alcalá de Henares, Madrid, Spain. manuelesteban.guil@salud.madrid.org.
Manuel
M
Guil-Cid
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. benito.fraile@uah.es.
Benito
B
Fraile
Department of Biomedicine and Biotechnology, University of Alcalá, 28871, Alcalá de Henares, Madrid, Spain. mar.royuela@uah.es.
Mar
M
Royuela
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D053148:Caspase 3 / Q000096:biosynthesis*; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011468:Prostatectomy / Q000639:trends*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D053148:Caspase 3