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

Abstract

This study aimed to assess the applicability of miR‐375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR‐375 levels by qRT‐PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR‐375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR‐375 levels were higher in the tumor stage group T3‐T4 compared with the T1‐T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease‐specific survival (DSS; p = 0.039). The combination of suPAR and miR‐375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10‐year overall survival (OS) and DSS, with a 6.38‐fold increased risk of death and a 7.68‐fold increased risk of tumor‐related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR‐375 showed a 5.72‐fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR‐375 levels in conjunction with the association of combined high suPAR/miR‐375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.

Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer

“…Wachet al reported in 2015 that the expression of miR-375 in 146 PCa patients (median: 1.214) was significantly higher than 35 BPH patients (median: 0.360) and 18 healthy controls (median: 0.405) [20]. Haldrup et al reported that miR-375 level was upregulated by 14.66-fold in serum samples from 31 PCa patients when compared to 13 BPH control patients (p=0.009) [21].…”

miR-375 induces docetaxel resistance in prostate cancer by targeting SEC23A and YAP1

“…Characterization of miRNA involvement likely facilitate predictive and prognostic markers of treatments as well as molecular targets for drug development in this stage and tumor type. miR-375 expression in tissue or circulation has been shown to potentially serve as a biomarker for PC diagnosis or prognosis [12–14]. We recently showed significant association of elevated miR-375 levels in plasma with poor overall survival of mCRPC patients [13].…”

The translational potential of microRNAs as biofluid markers of urological tumours

“…121,126 In nine out of these 15 miR-141-studies, miR-141 was only evaluated as a marker of advanced or metastatic prostate cancer (Table 3). 20,84,96,99,101,103,[113][114][115] but was frequently, if at all reported, not better than the routine marker PSA. 114,115,118 These data underline the fact that the clinical relevance of a marker can only be truly assessed if studies with similar questions are compared: a useful diagnostic marker might be a useless prognostic marker and vice versa.…”

“…88 (Table 3) report more promising diagnostic and prognostic data than earlier studies. One reason for this improvement could be that combinations of different miRNAs 111,121 , miRNAs in combination with other markers 113,120 and miRNAs in blood cells 123 or exosomes 124 were investigated, rather than single miRNAs. However, the promising results of these studies are yet to be validated.…”