Expression of progranulin (GP88) protein appears as an independent prognostic factor for clinical progression in high-risk prostate cancer patients

Abstract

Abstract Prostate cancer (PCa), the second most common cancer, is still a major cause of morbidity and mortality among men worldwide. A particularly aggressive group of PCa, where prognostic biomarkers are still needed, are clinically defined high-risk PCa. We had previously shown that the survival and proliferation factor progranulin (GP88) is a prognostic marker for primary PCa. We aimed in this study to characterize GP88 protein expression in high-risk PCa by immunohistochemistry and to examine its association with prognosis. Immunohistochemical staining for GP88 was performed with TMA of samples from 94 high-risk PCa patients using an H-score. GP88 staining was in a range of 3.69 to 252.51 (median: 109.28). The association of GP88 staining with prognosis was examined by survival analyses (Kaplan–Meier, multivariate Cox’s regression analysis). Elevated GP88 expression was associated with a shorter clinical progression-free survival (CPFS) in all PCa patients ( P  = 0.043), and in the following patient subgroups: Elder PCa patients (> 67 years; P  = 0.020), patients with pT3 tumors ( P  = 0.008), with Gleason scores GS5 and GS6 ( P  = 0.033 and P  = 0.030), and patients without radiation therapy ( P  = 0.009) at considering that only four patients received an adjuvant radiation therapy. In a multivariate Cox’s regression analysis, increased GP88 protein expression (RR = 2.98; P  = 0.049) and the preoperative PSA level (RR = 5.29; P  = 0.030) appeared as independent prognostic factors for clinical progression. Interestingly, lower GP88 staining in corresponding low Gleason lesions was correlated with the presence of immune cells, suggesting an immune cell suppressive effect of GP88. Altogether, Progranulin (GP88) protein positivity appears very likely to be an independent prognostic factor for clinical progression in high-risk PCa patients.