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

Abstract

Prostate cancer, the second most common cancer, is still a major cause of morbidity and mortality among men worldwide. The expression of the survival and proliferation factor progranulin (GP88) has not yet been comprehensively studied in PCa tumors. The aim of this study was to characterize GP88 protein expression in PCa by immunohistochemistry and to correlate the findings to the clinico-pathological data and prognosis. Immunohistochemical staining for GP88 was performed by TMA with samples from 442 PCa patients using an immunoreactive score (IRS). Altogether, 233 cases (52.7%) with negative GP88 staining (IRS < 2) and 209 cases (47.3%) with positive GP88 staining (IRS ≥ 2) were analyzed. A significant positive correlation was found for the GP88 IRS with the PSA value at prostatectomy and the cytoplasmic cytokeratin 20 IRS, whereas it was negatively associated with follow-up times. The association of GP88 staining with prognosis was further studied by survival analyses (Kaplan–Meier, univariate and multivariate Cox’s regression analysis). Increased GP88 protein expression appeared as an independent prognostic factor for overall, disease-specific and relapse-free survival in all PCa patients. Interestingly, in the subgroup of younger PCa patients (≤65 years), GP88 positivity was associated with a 3.8-fold (p = 0.004), a 6.0-fold (p = 0.008) and a 3.7-fold (p = 0.003) increased risk for death, disease-specific death and occurrence of a relapse, respectively. In the PCa subgroup with negative CK20 staining, GP88 positivity was associated with a 1.8-fold (p = 0.018) and a 2.8-fold increased risk for death and disease-specific death (p = 0.028). Altogether, GP88 protein positivity appears to be an independent prognostic factor for PCa patients.

Progranulin/EphA2 axis: A novel oncogenic mechanism in bladder cancer

“…Progranulin is implicated in several human diseases including cancer, neurodegenerative diseases, and rheumatoid arthritis [9,10]. Importantly, progranulin promotes in vivo tumorigenesis, and its elevated expression in various solid tumors correlates with an invasive phenotype and poor survival [9,[11][12][13][14][15][16]. Moreover, progranulin is a key adipokine that regulates insulin-resistance in adipose tissue [17].…”

Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients

“…For the study of GP88 protein expression, a manual IHC protocol was applied as previously described [ 29 ]. Briefly, after heat pretreatment at 120 °C for 5 min with TE–buffer pH 9 and peroxidase blocking (Dako, Hamburg, Germany), a primary antibody against GP88 (monoclonal mouse anti-GP88/PGRN antibody clone 6B3, Cat.…”

“…GP88, named after its molecular weight at ~88 kDa on Western immunoblots due to glycosylation, is physiologically a growth factor that regulates cell proliferation and wound repair, but pathologically it is also a component of the tumorigenesis machinery for different cancers [ 20 , 21 , 22 , 23 ]. Increased GP88 expression has been reported in breast cancer, brain tumors, non-small cell lung cancer, ovarian cancer, renal carcinoma, hepatocellular carcinoma, prostate cancer, colorectal cancer and hematological cancers [ 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. An association between increased GP88 protein expression and a poor prognosis has been reported for breast cancer, ovarian cancer, non-small cell lung carcinoma, lymphomas, esophageal cancer, prostate cancer, and colorectal cancer [ 25 , 26 , 28 , 29 , 30 , 31 , 32 ].…”

“…Increased GP88 expression has been reported in breast cancer, brain tumors, non-small cell lung cancer, ovarian cancer, renal carcinoma, hepatocellular carcinoma, prostate cancer, colorectal cancer and hematological cancers [ 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. An association between increased GP88 protein expression and a poor prognosis has been reported for breast cancer, ovarian cancer, non-small cell lung carcinoma, lymphomas, esophageal cancer, prostate cancer, and colorectal cancer [ 25 , 26 , 28 , 29 , 30 , 31 , 32 ]. GP88 expression is also correlated with resistance to anti-estrogen therapy in breast cancer patients [ 25 , 33 ] and platinum-based chemotherapy in non-small cell lung cancer patients [ 34 ].…”

Ist die Expression des GP88-Proteins (Progranulin) ein klinisch relevanter Prognosefaktor für Prostatakarzinompatienten?

“…In einer weiteren PCa-Patientenkohorte mit 442 Fällen untersuchten wir die GP88-Protein-Expression im Tumorgewebe mittels Immunhistochemie [22]. Die Auswertung erfolgte über einen immunreaktiven Score (IRS; Werte von 0-12; analog zu [23]…”