Class III beta-tubulin expression predicts prostate tumor aggressiveness and patient response to docetaxel-based chemotherapy.
Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human PCa cell lines using a human βIII-tubulin expression vector or βIII-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.
INSERM, Unité 955; Université Paris-Est, Faculté de Médecine; AP-HP, Groupe Henri Mondor-Albert Chenevier, Service d'Urologie, Département de Pathologie et Centre d'Investigations Biomédicales, Créteil, France. g.ploussard@gmail.com
Guillaume
G
Ploussard
Stéphane
S
Terry
Pascale
P
Maillé
Yves
Y
Allory
Nanor
N
Sirab
Laurence
L
Kheuang
Pascale
P
Soyeux
Nathalie
N
Nicolaiew
Estelle
E
Coppolani
Bernard
B
Paule
Laurent
L
Salomon
Stéphane
S
Culine
Ralph
R
Buttyan
Francis
F
Vacherot
Alexandre
A
de la Taille
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009919:Orchiectomy; D011379:Prognosis; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D014404:Tubulin / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel