Expression Profile of Autophagy-related Markers in Localized Prostate Cancer: Correlation With Biochemical Recurrence After Radical Prostatectomy

Abstract

To evaluate the expression of multiple molecular markers involved in autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in localized prostate cancer (PC) to clarify the prognostic significance of these markers in patients undergoing radical prostatectomy (RP). Expression levels of 5 autophagy markers, including autophagy-related gene 5, autophagy-related gene 9, Beclin1, microtubule-associated protein light chain 3, and UNC-51-like kinase 1 (ULK1), in RP specimens from 160 consecutive patients with clinically localized PC were measured by immunohistochemical staining. Of these 5 markers, ULK1 expression was significantly correlated with the incidence of biochemical recurrence (BR). On univariate analysis, ULK1 expression, serum prostate-specific antigen level, pathologic stage, Gleason score, seminal vesicle invasion, and surgical margin status were identified as significant predictors of BR. All these significant factors except for seminal vesicle invasion were independently associated with BR on multivariate analysis. Furthermore, significant differences in BR-free survival according to the positive numbers of these 5 independent risk factors were noted, that is, BR occurred in 2 of 33 patients negative for risk factors (6.1%), 20 of 76 patients positive for 1 or 2 risk factors (26.3%), and 38 of 51 patients positive for≥3 risk factors (74.5%). Collectively, these findings suggest that measurement of expression levels of potential autophagy markers, particularly ULK1, in RP specimens, in addition to conventional parameters, may contribute to the accurate prediction of BR after RP for localized PC.