Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
PLoS ONE (Impact Factor: 3.23). 07/2013; 8(7):e69239. DOI: 10.1371/journal.pone.0069239
Source: PubMed


MicroRNAs (miRNAs) are small (∼22 nucleotide) non-coding RNAs that regulate a myriad of biological processes and are frequently dysregulated in cancer. Cancer-associated microRNAs have been detected in serum and plasma and hold promise as minimally invasive cancer biomarkers, potentially for assessing disease characteristics in patients with metastatic disease that is difficult to biopsy. Here we used miRNA profiling to identify cancer-associated miRNAs that are differentially expressed in sera from patients with metastatic castration resistant prostate cancer (mCRPC) as compared to healthy controls. Of 365 miRNAs profiled, we identified five serum miRNAs (miR-141, miR-200a, miR-200c, miR-210 and miR-375) that were elevated in cases compared to controls across two independent cohorts. One of these, miR-210, is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. Exposure of cultured prostate cancer cells to hypoxia led to induction of miR-210 and its release into the extracellular environment. Moreover, we found that serum miR-210 levels varied widely amongst mCRPC patients undergoing therapy, and correlated with treatment response as assessed by change in PSA. Our results suggest that (i) cancer-associated hypoxia is a frequent, previously under-appreciated characteristic of mCRPC, and (ii) serum miR-210 may be further developed as a predictive biomarker in patients with this distinct disease biology.

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Available from: Arul M Chinnaiyan, Feb 19, 2014
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    • "Only a few studies have investigated the levels of (circulating) miRNAs as therapeutic markers. The investigations that evaluated potential biomarkers in metastatic PCa and/or CRPC are limited by the number of patients and tested miRNAs [9, 109–111, 118]. In these studies, the researcher investigated upregulated circulating miRNAs in serum of CRPC patients that are applicable candidates as markers for therapeutic response. "
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    BioMed Research International 08/2014; 2014:591703. DOI:10.1155/2014/591703 · 2.71 Impact Factor
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    British Journal of Cancer 04/2014; 110(10). DOI:10.1038/bjc.2014.181 · 4.84 Impact Factor
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    ABSTRACT: Abstract This review focuses on the promising potential of nucleic acids in body fluids such as blood and urine as diagnostic, prognostic, predictive and monitoring biomarkers in urologic malignancies. The tremendous progress in the basic knowledge of molecular processes in cancer, as shown in the companion review on nucleic acid-based biomarkers in tissue of urologic tumors, provides a strong rationale for using these molecular changes as non-invasive markers in body fluids. The changes observed in body fluids are an integrative result, reflecting both tissue changes and processes occurring in the body fluids. The availability of sensitive methods has only recently made possible detailed studies of DNA- and RNA-based markers in body fluids. In addition to these biological aspects, methodological aspects of the determination of nucleic acids in body fluids, i.e. pre-analytical, analytical and post-analytical issues, are particularly emphasized. The characteristic changes of RNA (differential mRNA and miRNA expression) and DNA (concentrations, integrity index, mutations, microsatellite and methylation alterations) in serum/plasma and urine samples of patients suffering from the essential urologic cancers of the prostate, bladder, kidney and testis are summarized and critically discussed below. To translate the promising results into clinical practice, laboratory scientists and clinicians have to collaborate to resolve the challenges of harmonized and feasible pre-analytical and analytical conditions for the selected markers and to validate these markers in well-designed and sufficiently powered multi-center studies.
    Critical Reviews in Clinical Laboratory Sciences 05/2014; 51(4):1-32. DOI:10.3109/10408363.2014.914888 · 3.69 Impact Factor
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