Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low‐risk, localized prostate cancer

Abstract

Background Recent studies show that microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, may have potential for monitoring cancer status. We investigated circulating miRNAs in prostate cancer that may be associated with the progression of hormone-sensitive primary tumors to metastatic castration resistant prostate cancer (CRPC) after androgen deprivation therapy. Methods Using genome-wide expression profiling by TaqMan Human MicroRNA Arrays (Applied Biosystems) and/or quantitative real-time polymerase chain reaction, we compared the expression levels of miRNAs in serum samples from 28 patients of low-risk localized disease, 30 of high-risk localized disease and 26 of metastatic CRPC. Results we demonstrated that serum samples from patients of low-risk, localized prostate cancer and metastatic CRPC patients exhibit distinct circulating miRNA signatures. MiR-375, miR-378*, and miR-141 were significantly over-expressed in serum from CRPC patients compared to serum from low-risk localized patients, while miR-409-3p was significantly under-expressed. In prostate primary tumor samples, miR-375 and miR-141 also had significantly higher expression levels compared to those in normal prostate tissue. Conclusions Circulating microRNAs, particularly miR-375, miR-141, miR-378* and miR-409-3p, are differentially expressed in serum samples from prostate cancer patients. In the search for improved minimally invasive methods to follow cancer pathogenesis, the correlation of disease status with the expression patterns of circulating miRNAs may indicate the potential importance of circulating miRNAs as prognostic markers for prostate cancer progression.

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

“…This increase in miR-375 was initially reported in our earlier study (5), as well as by Schaefer and colleagues (24) and Martens-Uzunova and colleagues (25). Two recent studies reported increased serum levels of miR-375 (and miR-141) in patients with metastatic prostate carcinoma (26,27). In contrast, a miRNA profiling approach based on high-throughput sequencing by Watahiki and colleagues did not find an increase of miR-375 in metastatic prostate carcinoma (28).…”

“…Recent data also describe elevated serum levels of miR-375 and miR-141 as predictors for poor prognosis (27) or metastasis (26) reviewed in reference 6. MiR-141 is found upregulated in primary tissues in a variety of studies including ours (2,25), and inclusion of miRNA expression data significantly improves the accuracy of markers like prostatespecific antigen in the diagnosis or prediction of tumor outcome (33).…”

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.…”

Application of omic technologies in cancer research

“…An example of this are the miR-141 and miR-375, which have been detected at significantly greater levels in metastatic compared to non-metastatic prostate cancer. 8,9 Although investigating the transcriptome can provide some valuable insight into biology (phenotype), the socalled machinery driving the biology of the cell and organism are the proteins (the proteome). The link between transcriptional activity and the proteome is not necessarily direct, and so the definition of the biology and the identification of drivers of disease and therapeutic resistance require multiple omics-based approaches.…”