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A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue
Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
Cancer Genome Research Group, Division of Molecular Genetics, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases, Heidelberg 69120, Germany
Department of Pathology, Medical Center, University of Rostock, Rostock 18055, Germany
These authors contributed equally to this paper.
* Author to whom correspondence should be addressed.
Received: 7 January 2013; in revised form: 30 January 2013 / Accepted: 27 February 2013 / Published: 4 March 2013
Abstract: We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.
Keywords: prostate carcinoma; tumor neighboring normal tissue; microRNA; molecular marker; early neoplastic transformation; field cancerization
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Hellwinkel, O.J.C.; Sellier, C.; Sylvester, Y.-M.J.; Brase, J.C.; Isbarn, H.; Erbersdobler, A.; Steuber, T.; Sültmann, H.; Schlomm, T.; Wagner, C. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue. Int. J. Mol. Sci. 2013, 14, 5239-5249.
Hellwinkel OJC, Sellier C, Sylvester Y-MJ, Brase JC, Isbarn H, Erbersdobler A, Steuber T, Sültmann H, Schlomm T, Wagner C. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue. International Journal of Molecular Sciences. 2013; 14(3):5239-5249.
Hellwinkel, Olaf J.C.; Sellier, Christina; Sylvester, Yu-Mi J.; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina. 2013. "A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue." Int. J. Mol. Sci. 14, no. 3: 5239-5249.