title: Predictive and prognostic values of Tau and BubR1 protein in prostate cancer and their relationship to the Gleason score.
abstract: The aim of this study is to detect the expression levels of spindle assembly checkpoint protein-BubR1 and microtubule-associated protein-Tau in human prostate cancer tissues of different Gleason score, and to test whether there is a relationship between their expression levels and clinicopathologic parameters including response to docetaxel treatment, Gleason score, and overall survival (OS). Moreover, to test whether Tau protein expressed in the cancerous prostate tissue is phosphorylated. Thirty patients who received at least three cycles docetaxel for metastatic castrate-resistant prostate cancer were included into the trial. The patients' formalin-fixed and paraffin-embedded prostate tissue specimens were retrospectively obtained from the pathology department archives of Ege University School of Medicine. The expression status of BubR1 protein was defined by immunohistochemical (IHC) using the anti-BubR1 antibody. The expression status of Tau protein was defined by IHC using the two types of Tau antibodies: anti-Tau-1 antibody (that recognizes Tau only in its dephosphorylated form) and anti-PHF-Tau antibody (that recognizes all isoforms of human Tau proteins independent of its phosphorylation status). The BubR1 and Tau were overexpressed in about 63 and 23 % of the study group, respectively. Tau overexpression was significantly associated with lower Gleason score. There was no significant association between the expression levels of BubR1 and Tau proteins, and docetaxel response. Reduced BubR1 expression was strongly associated with longer survival (P = 0.008), whereas Tau expression status did not effect survival. Moreover, the Tau expression of cancerous prostate tissue was highly dephosphorylated. In this clinicopathological study, our findings did not confirm the preclinical observations that low BubR1 and Tau expression confer selective sensitivity to microtubulisin drugs. Our data imply that reduced BubR1 expression was a predictor for longer OS, and the possibility that high Tau expression may be involved in better prognosis due to its relationship to the Gleason score. Furthermore, our data suggest that both Tau and BubR1 may be a promising prognostic marker rather than predictive marker in patients with prostate cancer.
authors.affiliation: Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege Universtiy, Bornova, 35100 Izmir, Turkey. yalcincrk@gmail.com
authors.forename: Yalcin
authors.initials: Y
authors.lastname: Cirak
authors.forename: Banu
authors.initials: B
authors.lastname: Sarsik
authors.forename: Burcu
authors.initials: B
authors.lastname: Cakar
authors.forename: Sait
authors.initials: S
authors.lastname: Sen
authors.forename: Adnan
authors.initials: A
authors.lastname: Simsir
authors.forename: Ruchan
authors.initials: R
authors.lastname: Uslu
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000077143:Docetaxel; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C054369:MAPT protein, human; D043823:Taxoids; D016875:tau Proteins; D000077143:Docetaxel; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases