Expression of GP88 (progranulin) in serum of prostate cancer patients is associated with Gleason scores and overall survival

Abstract

BackgroundGP88/Progranulin is a well-recognized cell growth promoter in different cancers, and elevated serum GP88 levels have been described as negative prognostic factor in breast cancer. However, serum levels in prostate cancer (PCa) patients have not yet been studied.Material and MethodsWe analyzed serum GP88 levels by enzyme immunosorbent assay and correlated them with clinicopathological parameters in PCa patients. PCa patients were separated into two groups based on the serum GP88 median level (low ≤44.56 ng/mL or high >44.56 ng/mL) and according to their median age (younger ≤66 years or elder patients >66 years).ResultsLow serum GP88 levels were more often detected in younger patients and high levels in elder patients (P=0.018; Fisher’s exact test). PCa patients were separated into three groups, Gleason score (GS) ≤6; GS=7; and GS≥8. In receiver operating characteristic analyses, we could distinguish GS≤6 from GS=7 [area under the curve (AUC): 0.646; P=0.018] and GS≤6 from GS≥8 (AUC: 0.629; P=0.048) but not GS=7 from GS≥8. For survival analysis, GP88 levels were separated into two groups by an optimized cutoff value of 36.92 ng/mL. Using this GP88 stratification, all PCa patients and younger patients with a low serum GP88 level had a significantly better overall survival compared with patients with higher serum GP88 levels (log-rank test P=0.010 and P=0.024).ConclusionSerum GP88 levels are significantly different depending on age and GS, and they are associated with the prognosis of PCa patients.

Expression of GP88 (Progranulin) Protein Is an Independent Prognostic Factor in Prostate Cancer Patients

“…We showed, for the first time, that increased GP88 protein expression (IRS ≥ 2) in PCa tumor tissues is an independent prognostic marker for shorter OS, DSS and RFS in PCa patients. Previously, we reported that serum GP88 expression was an independent prognostic factor for OS in PCa patients [19]. Interestingly, we show here that GP88 protein expression appeared to be an independent prognostic factor for OS, DSS and RFS only in the younger patient group (≤65 years) but not in the older patient group (>65 years).…”

“…In addition, in PCa patients with CK20-negative staining (IRS < 2), GP88 positivity was an independent parameter for OS and DSS. Considering that we have found, in a separate study [19], that serum GP88 levels were also associated with clinical outcomes, particularly in younger PCa patients, the combination of GP88 measurements in tumor biopsies and in serum would provide cost-effective assays to improve the management of PCa patients. Future studies measuring serum and tissue GP88 in PCa patients would allow us to explore this possibility.…”

“…The expression of GP88 protein was positively correlated with the PSA value at prostatectomy and cytoplasmic cytokeratin 20 (CK20) staining; moreover, increased GP88 in tumor tissue was a prognostic factor because it was correlated with shorter follow-up times for overall, disease-specific and relapse-free survival. Our previous study investigating the serum GP88 levels in prostate cancer patients [19] reported that serum GP88 levels were different between tumor stage and age groups; i.e., low GP88 levels were more often observed in lower tumor stage groups (pT1/pT2) and in the early age group (≤66 years), and vice versa, increased GP88 levels were more often observed in the higher tumor stage group (pT3/pT4) and in the older age group (>66 years). In the current study, GP88 expression was different in PSA level groups, i.e., low GP88 levels were more often found in the low PSA group (<4 ng/mL), and vice versa, increased GP88 levels were more often found in the higher PSA group (≥4 ng/mL).…”

“…In vitro GP88 promotes cell growth, migration, invasion and anchorage-independent growth in prostate cancer cells [18]. Recently, we investigated the circulating levels of GP88 in the serum of prostate cancer patients and showed that all PCa patients and particularly younger PCa patients with a low serum GP88 level had a significantly better overall survival compared with that of patients with higher serum GP88 levels [19]. In the present study, we examined GP88 protein expression in PCa tissue and its correlation with clinico-pathological data and the prognosis of PCa patients.…”

Association of Serum Progranulin Levels With Disease Progression, Therapy Response and Survival in Patients With Metastatic Breast Cancer

“…43 Increased tumor tissue GP88 and serum levels have been found to be associated with poor outcomes in nonesmall-cell lung carcinoma, 46 and serum GP88 was associated with Gleason score and poor outcome in patients with advanced prostate cancer. 47 Interestingly, increase of GP88 level in cerebrospinal fluid was reported in patients with cancer with central nervous system (CNS) metastasis compared with patients without CNS metastasis, 48 suggesting that this could be used as an approach to detect CNS metastases, which are sometimes difficult to determine by imaging. The present paper was focused in examining the association of serum GP88 level in stage 4 patients with BC with survival and whether measuring serum GP88 level could be used to monitor patient response to therapy or progression Progranulin and Metastatic Breast Cancer of disease.…”