Association of Tissue mRNA and Serum Antigen Levels of Members of the Urokinase-Type Plasminogen Activator System with Clinical and Prognostic Parameters in Prostate Cancer

Abstract

The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uPA mRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Cox's regression analysis; HR = 7.12, P = 0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.

The combined serum levels ofmiR-375and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer

“…]). Recently, we showed in an independent PCa patient cohort that high suPAR protein levels in the serum were associated with a sevenfold increased risk of death compared with patients with low/intermediate levels . Our results confirmed previous findings of a significant association between elevated suPAR levels in blood and a poor outcome .…”

PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives

“…Riddick et al [28] used qPCR and found increased mRNA expression in malignant tissue samples from patients with PC compared to non-malignant samples from patients with benign prostatic hyperplasia with statistically significant positive correlations with Gleason score. However, this could not be confirmed in the study by Al-Jabani et al [27], where increased mRNA expression levels of uPA and PAI-1 and not uPAR were found in PC tissue compared to benign prostate hyperplasia and normal prostate tissue.…”

“…Similar to the immunohistochemical analysis, uPAR expression at mRNA level has only been investigated in a limited number of studies and only in small populations of PC patients, using either in situ hybridization or real-time quantitative PCR (qPCR) [22, 23, 27, 28]. Riddick et al [28] used qPCR and found increased mRNA expression in malignant tissue samples from patients with PC compared to non-malignant samples from patients with benign prostatic hyperplasia with statistically significant positive correlations with Gleason score.…”

“…In addition, pre-operative circulating total uPAR levels were found to be higher among patients with higher biopsy Gleason grade, extraprostatic extension, and lymph node positive disease after radical prostatectomy, and, indeed, PC patients with bone metastasis exhibited significantly higher uPAR levels compared with patients with localized disease or patients with lymph node metastasis [30]. Furthermore, studies have found significantly lowered overall survival rate of PC patients with high plasma levels of uPAR compared with low serum uPAR levels [27, 29]. In the most recently published study, the plasma levels of the cleaved uPAR forms, uPAR(I–III) + uPAR(II–III) and uPAR(I) levels, were significantly higher, while level of intact uPAR(I–III) did not differ, in hormone-naive and castrate-resistant patients compared with patients with localized disease, highlighting that analysis of the cleaved forms might be superior and, thus, provide additional prognostic and predictive information [31].…”

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) Complexes for Targeting uPAR in Prostate Cancer

“…48,62–66 Increased expression of uPAR has been associated with more aggressive and advanced CaP relative to indolent or localized disease. 63,67–71 Developing uPAR-targeted analogs labeled with SPECT radionuclides would be desirable to aid CaP assessment in patients. In the present study, the 99m Tc-labeled AE015 peptide was utilized in binding assays in vitro with PC-3 cells and in biodistribution analyses in vivo with mice bearing PC-3 xenografts.…”