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Prostate Cancer
Volume 2013 (2013), Article ID 539680, 10 pages
http://dx.doi.org/10.1155/2013/539680
Review Article
Circulating MicroRNAs as Biomarkers of Prostate Cancer: The State of Play
1Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Level 5 Clinical Sciences Building, Parkville, Melbourne, VIC 3050, Australia
2Dame Roma Mitchell Cancer Research Laboratories, The University of Adelaide, P.O. Box 14, Rundle Mall, Adelaide, SA 5000, Australia
Received 28 September 2012; Accepted 5 February 2013
Academic Editor: Jostein Halgunset
Copyright © 2013 Nikhil Sapre and Luke A. Selth. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Linked References
- F. Bray, J.-S. Ren, E. Masuyer, and J. Ferlay, “Global estimates of cancer prevalence for 27 sites in the adult population in 2008,” International Journal of Cancer, vol. 132, no. 5, pp. 1133–1145, 2013. View at Publisher · View at Google Scholar
- J. E. Oesterling, “Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate,” Journal of Urology, vol. 145, no. 5, pp. 907–923, 1991. View at Scopus
- W. J. Catalona, D. S. Smith, T. L. Ratliff et al., “Measurement of prostate-specific antigen in serum as a screening test for prostate cancer,” The New England Journal of Medicine, vol. 324, no. 17, pp. 1156–1161, 1991. View at Scopus
- I. M. Thompson, D. K. Pauler, P. J. Goodman et al., “Prevalence of prostate cancer among men with a prostate-specific antigen level ≤ 4.0 ng per milliliter,” The New England Journal of Medicine, vol. 350, no. 22, pp. 2239–2346, 2004. View at Publisher · View at Google Scholar · View at Scopus
- J. Hugosson, S. Carlsson, G. Aus et al., “Mortality results from the Göteborg randomised population-based prostate-cancer screening trial,” The Lancet Oncology, vol. 11, no. 8, pp. 725–732, 2010. View at Publisher · View at Google Scholar · View at Scopus
- F. H. Schröder, J. Hugosson, M. J. Roobol et al., “Screening and prostate-cancer mortality in a randomized european study,” The New England Journal of Medicine, vol. 360, no. 13, pp. 1320–1328, 2009. View at Publisher · View at Google Scholar · View at Scopus
- G. L. Andriole, E. D. Crawford, R. L. Grubb III et al., “Mortality results from a randomized prostate-cancer screening trial,” The New England Journal of Medicine, vol. 360, no. 13, pp. 1310–1319, 2009. View at Publisher · View at Google Scholar
- M. Sánchez-Chapado, G. Olmedilla, M. Cabeza, E. Donat, and A. Ruiz, “Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study,” Prostate, vol. 54, no. 3, pp. 238–247, 2003. View at Publisher · View at Google Scholar · View at Scopus
- K. Stamatiou, A. Alevizos, E. Agapitos, and F. Sofras, “Incidence of impalpable carcinoma of the prostate and of non-malignant and precarcinomatous lesions in Greek male population: an autopsy study,” Prostate, vol. 66, no. 12, pp. 1319–1328, 2006. View at Publisher · View at Google Scholar · View at Scopus
- P. C. Albertsen, J. A. Hanley, D. F. Gleason, and M. J. Barry, “Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer,” Journal of the American Medical Association, vol. 280, no. 11, pp. 975–980, 1998. View at Publisher · View at Google Scholar · View at Scopus
- P. Mufarrij, A. Sankin, G. Godoy, and H. Lepor, “Pathologic outcomes of candidates for active surveillance undergoing radical prostatectomy,” Urology, vol. 76, no. 3, pp. 689–692, 2010. View at Publisher · View at Google Scholar
- G. Attard and J. S. De Bono, “Translating scientific advancement into clinical benefit for castration-resistant prostate cancer patients,” Clinical Cancer Research, vol. 17, no. 12, pp. 3867–3875, 2011. View at Publisher · View at Google Scholar · View at Scopus
- K. A. Phillips, S. Van Bebber, and A. M. Issa, “Diagnostics and biomarker development: priming the pipeline,” Nature Reviews Drug Discovery, vol. 5, no. 6, pp. 463–469, 2006. View at Publisher · View at Google Scholar · View at Scopus
- R. C. Lee, R. L. Feinbaum, and V. Ambros, “The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14,” Cell, vol. 75, no. 5, pp. 843–854, 1993. View at Publisher · View at Google Scholar · View at Scopus
- D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
- J. Winter, S. Jung, S. Keller, R. I. Gregory, and S. Diederichs, “Many roads to maturity: microRNA biogenesis pathways and their regulation,” Nature Cell Biology, vol. 11, no. 3, pp. 228–234, 2009. View at Publisher · View at Google Scholar · View at Scopus
- Y. Lee, C. Ahn, J. Han et al., “The nuclear RNase III Drosha initiates microRNA processing,” Nature, vol. 425, no. 6956, pp. 415–419, 2003. View at Publisher · View at Google Scholar · View at Scopus
- E. Lund, S. Güttinger, A. Calado, J. E. Dahlberg, and U. Kutay, “Nuclear export of microRNA precursors,” Science, vol. 303, no. 5654, pp. 95–98, 2004. View at Publisher · View at Google Scholar · View at Scopus
- R. Yi, Y. Qin, I. G. Macara, and B. R. Cullen, “Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs,” Genes and Development, vol. 17, no. 24, pp. 3011–3016, 2003. View at Publisher · View at Google Scholar · View at Scopus
- R. C. Friedman, K. K. H. Farh, C. B. Burge, and D. P. Bartel, “Most mammalian mRNAs are conserved targets of microRNAs,” Genome Research, vol. 19, no. 1, pp. 92–105, 2009. View at Publisher · View at Google Scholar · View at Scopus
- B. P. Lewis, C. B. Burge, and D. P. Bartel, “Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets,” Cell, vol. 120, no. 1, pp. 15–20, 2005. View at Publisher · View at Google Scholar · View at Scopus
- A. Kozomara and S. Griffiths-Jones, “MiRBase: integrating microRNA annotation and deep-sequencing data,” Nucleic Acids Research, vol. 39, no. 1, pp. D152–D157, 2011. View at Publisher · View at Google Scholar · View at Scopus
- R. Zhang and B. Su, “Small but influential: the role of microRNAs on gene regulatory network and 3′UTR evolution,” Journal of Genetics and Genomics, vol. 36, no. 1, pp. 1–6, 2009. View at Publisher · View at Google Scholar · View at Scopus
- G. A. Calin, C. D. Dumitru, M. Shimizu et al., “Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15524–15529, 2002. View at Publisher · View at Google Scholar · View at Scopus
- C. M. Croce, “Causes and consequences of microRNA dysregulation in cancer,” Nature Reviews Genetics, vol. 10, no. 10, pp. 704–714, 2009. View at Publisher · View at Google Scholar · View at Scopus
- A. Schaefer, C. Stephan, J. Busch, G. M. Yousef, and K. Jung, “Diagnostic, prognostic and therapeutic implications of microRNAs in urologic tumors,” Nature Reviews Urology, vol. 7, no. 5, pp. 286–297, 2010. View at Publisher · View at Google Scholar · View at Scopus
- R. Ma, T. Jiang, and X. Kang, “Circulating microRNAs in cancer: origin, function and application,” Journal of Experimental and Clinical Cancer Research, vol. 31, no. 1, article 38, 2012. View at Publisher · View at Google Scholar
- Y. Karube, H. Tanaka, H. Osada et al., “Reduced expression of Dicer associated with poor prognosis in lung cancer patients,” Cancer Science, vol. 96, no. 2, pp. 111–115, 2005. View at Publisher · View at Google Scholar · View at Scopus
- M. S. Kumar, R. E. Pester, C. Y. Chen et al., “Dicer1 functions as a haploinsufficient tumor suppressor,” Genes and Development, vol. 23, no. 23, pp. 2700–2704, 2009. View at Publisher · View at Google Scholar · View at Scopus
- R. Koesters, V. Adams, D. Betts et al., “Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression,” Genomics, vol. 61, no. 2, pp. 210–218, 1999. View at Publisher · View at Google Scholar · View at Scopus
- L. Li, C. Yu, H. Gao, and Y. Li, “Argonaute proteins: potential biomarkers for human colon cancer,” BMC Cancer, vol. 10, article no. 38, 2010. View at Publisher · View at Google Scholar · View at Scopus
- D. Qiao, A. M. Zeeman, W. Deng, L. H. J. Looijenga, and H. Lin, “Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas,” Oncogene, vol. 21, no. 25, pp. 3988–3999, 2002. View at Publisher · View at Google Scholar · View at Scopus
- J. Lu, G. Getz, E. A. Miska et al., “MicroRNA expression profiles classify human cancers,” Nature, vol. 435, no. 7043, pp. 834–838, 2005. View at Publisher · View at Google Scholar · View at Scopus
- M. V. Iorio, M. Ferracin, C. G. Liu et al., “MicroRNA gene expression deregulation in human breast cancer,” Cancer Research, vol. 65, no. 16, pp. 7065–7070, 2005. View at Publisher · View at Google Scholar · View at Scopus
- M. V. Iorio, R. Visone, G. Di Leva et al., “MicroRNA signatures in human ovarian cancer,” Cancer Research, vol. 67, no. 18, pp. 8699–8707, 2007. View at Publisher · View at Google Scholar · View at Scopus
- P. S. Mitchell, R. K. Parkin, E. M. Kroh et al., “Circulating microRNAs as stable blood-based markers for cancer detection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 30, pp. 10513–10518, 2008. View at Publisher · View at Google Scholar · View at Scopus
- L. A. Selth, S. Townley, J. L. Gillis et al., “Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease,” International Journal of Cancer, vol. 131, no. 3, pp. 652–661, 2012. View at Publisher · View at Google Scholar
- S. S. C. Chim, T. K. F. Shing, E. C. W. Hung et al., “Detection and characterization of placental microRNAs in maternal plasma,” Clinical Chemistry, vol. 54, no. 3, pp. 482–490, 2008. View at Publisher · View at Google Scholar · View at Scopus
- C. H. Lawrie, S. Gal, H. M. Dunlop et al., “Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma,” British Journal of Haematology, vol. 141, no. 5, pp. 672–675, 2008. View at Publisher · View at Google Scholar · View at Scopus
- L. A. Selth, W. D. Tilley, and L. M. Butler, “Circulating microRNAs: macro-utility as markers of prostate cancer?” Endocrine-Related Cancer, vol. 19, no. 4, pp. R99–R113, 2012. View at Publisher · View at Google Scholar
- X. Chen, Y. Ba, L. Ma et al., “Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases,” Cell Research, vol. 18, no. 10, pp. 997–1006, 2008. View at Publisher · View at Google Scholar · View at Scopus
- J. D. Arroyo, J. R. Chevillet, E. M. Kroh et al., “Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 12, pp. 5003–5008, 2011. View at Publisher · View at Google Scholar · View at Scopus
- H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee, and J. O. Lötvall, “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,” Nature Cell Biology, vol. 9, no. 6, pp. 654–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
- K. C. Vickers, B. T. Palmisano, B. M. Shoucri, R. D. Shamburek, and A. T. Remaley, “MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins,” Nature Cell Biology, vol. 13, no. 4, pp. 423–433, 2011. View at Publisher · View at Google Scholar · View at Scopus
- J. Skog, T. Würdinger, S. van Rijn et al., “Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers,” Nature Cell Biology, vol. 10, no. 12, pp. 1470–1476, 2008. View at Publisher · View at Google Scholar · View at Scopus
- M. A. Cortez, C. Bueso-Ramos, J. Ferdin, G. Lopez-Berestein, A. K. Sood, and G. A. Calin, “MicroRNAs in body fluids-the mix of hormones and biomarkers,” Nature Reviews Clinical Oncology, vol. 8, no. 8, pp. 467–477, 2011. View at Publisher · View at Google Scholar · View at Scopus
- Y. Zhang, D. Liu, X. Chen et al., “Secreted monocytic miR-150 enhances targeted endothelial cell migration,” Molecular Cell, vol. 39, no. 1, pp. 133–144, 2010. View at Publisher · View at Google Scholar · View at Scopus
- J. A. Weber, D. H. Baxter, S. Zhang et al., “The microRNA spectrum in 12 body fluids,” Clinical Chemistry, vol. 56, no. 11, pp. 1733–1741, 2010. View at Publisher · View at Google Scholar · View at Scopus
- M. Hanke, K. Hoefig, H. Merz et al., “A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer,” Urologic Oncology, vol. 28, no. 6, pp. 655–661, 2010. View at Publisher · View at Google Scholar · View at Scopus
- N. J. Park, H. Zhou, D. Elashoff et al., “Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection,” Clinical Cancer Research, vol. 15, no. 17, pp. 5473–5477, 2009. View at Publisher · View at Google Scholar
- M. J. Lodes, M. Caraballo, D. Suciu, S. Munro, A. Kumar, and B. Anderson, “Detection of cancer with serum miRNAs on an oligonucleotide microarray,” PLoS ONE, vol. 4, no. 7, Article ID e6229, 2009. View at Publisher · View at Google Scholar
- F. Moltzahn, A. B. Olshen, L. Baehner et al., “Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients,” Cancer Research, vol. 71, no. 2, pp. 550–560, 2011. View at Publisher · View at Google Scholar · View at Scopus
- J. C. Brase, M. Johannes, T. Schlomm et al., “Circulating miRNAs are correlated with tumor progression in prostate cancer,” International Journal of Cancer, vol. 128, no. 3, pp. 608–616, 2011. View at Publisher · View at Google Scholar
- J. C. Gonzales, L. M. Fink, O. B. Goodman Jr., J. T. Symanowski, N. J. Vogelzang, and D. C. Ward, “Comparison of circulating MicroRNA 141 to circulating tumor cells, lactate dehydrogenase, and prostate-specific antigen for determining treatment response in patients with metastatic prostate cancer,” Clinical Genitourinary Cancer, vol. 9, no. 1, pp. 39–45, 2011. View at Publisher · View at Google Scholar
- F. Y. Agaoglu, M. Kovancilar, Y. Dizdar et al., “Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer,” Tumour Biology, vol. 32, no. 3, pp. 583–588, 2011. View at Publisher · View at Google Scholar · View at Scopus
- R. Mahn, L. C. Heukamp, S. Rogenhofer, A. Von Ruecker, S. C. Müller, and J. Ellinger, “Circulating microRNAs (miRNA) in serum of patients with prostate cancer,” Urology, vol. 77, no. 5, pp. 1265–e9, 2011. View at Publisher · View at Google Scholar · View at Scopus
- R. J. Bryant, T. Pawlowski, J. W. F. Catto et al., “Changes in circulating microRNA levels associated with prostate cancer,” British Journal of Cancer, vol. 106, no. 4, pp. 768–774, 2012. View at Publisher · View at Google Scholar
- H. C. N. Nguyen, W. Xie, M. Yang et al., “Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer,” Prostate, vol. 73, no. 4, pp. 346–354, 2013. View at Publisher · View at Google Scholar
- Z.-H. Chen, G.-L. Zhang, H.-R. Li et al., “A panel of five circulating microRNAs as potential biomarkers for prostate cancer,” Prostate, vol. 72, no. 13, pp. 1443–1452, 2012. View at Publisher · View at Google Scholar
- C. Zheng, S. Yinghao, and J. Li, “MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by targeting DVL2,” Medical Oncology, vol. 29, no. 2, pp. 815–822, 2012. View at Publisher · View at Google Scholar
- J. Shen, G. W. Hruby, J. M. McKiernan et al., “Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer,” Prostate, vol. 72, no. 13, pp. 1469–1477, 2012. View at Publisher · View at Google Scholar
- I. Sanders, S. Holdenrieder, G. Walgenbach-Brünagel et al., “Evaluation of reference genes for the analysis of serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma,” International Journal of Urology, vol. 19, no. 11, pp. 1017–1025, 2012. View at Publisher · View at Google Scholar
- J. C. Brase, D. Wuttig, R. Kuner, and H. Sültmann, “Serum microRNAs as non-invasive biomarkers for cancer,” Molecular Cancer, vol. 9, article no. 306, 2010. View at Publisher · View at Google Scholar · View at Scopus
- H. L. Zhang, L. F. Yang, Y. Zhu et al., “Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy,” Prostate, vol. 71, no. 3, pp. 326–331, 2011. View at Publisher · View at Google Scholar · View at Scopus
- D. Hessels, J. M. T. Klein Gunnewiek, I. Van Oort et al., “DD-based molecular urine analysis for the diagnosis of prostate cancer,” European Urology, vol. 44, no. 1, pp. 8–16, 2003. View at Publisher · View at Google Scholar
- J. Szczyrba, E. Löprich, S. Wach et al., “The microRNA profile of prostate carcinoma obtained by deep sequencing,” Molecular Cancer Research, vol. 8, no. 4, pp. 529–538, 2010. View at Publisher · View at Google Scholar · View at Scopus
- H. Cheng, L. Zhang, D. E. Cogdell et al., “Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis,” PLoS One, vol. 6, no. 3, Article ID e17745, 2011. View at Publisher · View at Google Scholar · View at Scopus
- L. M. Li, Z. B. Hu, Z. X. Zhou et al., “Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma,” Cancer Research, vol. 70, no. 23, pp. 9798–9807, 2010. View at Publisher · View at Google Scholar · View at Scopus
- R. Duttagupta, R. Jiang, J. Gollub, R. C. Getts, and K. W. Jones, “Impact of cellular miRNAs on circulating miRNA biomarker signatures,” PLoS One, vol. 6, no. 6, Article ID e20769, 2011. View at Publisher · View at Google Scholar · View at Scopus
- J. S. McDonald, D. Milosevic, H. V. Reddi, S. K. Grebe, and A. Algeciras-Schimnich, “Analysis of circulating microRNA: preanalytical and analytical challenges,” Clinical Chemistry, vol. 57, no. 6, pp. 833–840, 2011. View at Publisher · View at Google Scholar · View at Scopus
- M. B. Kirschner, S. C. Kao, J. J. Edelman et al., “Haemolysis during sample preparation alters microRNA content of plasma,” PLoS One, vol. 6, no. 9, Article ID e24145, 2011. View at Publisher · View at Google Scholar
- L. J. Sokoll, W. Ellis, P. Lange et al., “A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance, and diagnostic accuracy,” Clinica Chimica Acta, vol. 389, no. 1-2, pp. 1–6, 2008. View at Publisher · View at Google Scholar · View at Scopus
- E. M. Kroh, R. K. Parkin, P. S. Mitchell, and M. Tewari, “Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR),” Methods, vol. 50, no. 4, pp. 298–301, 2010. View at Publisher · View at Google Scholar · View at Scopus
- L. W. Lee, S. Zhang, A. Etheridge et al., “Complexity of the microRNA repertoire revealed by next-generation sequencing,” RNA, vol. 16, no. 11, pp. 2170–2180, 2010. View at Publisher · View at Google Scholar · View at Scopus
- B. M. Ryan, A. I. Robles, and C. C. Harris, “Genetic variation in microRNA networks: the implications for cancer research,” Nature Reviews Cancer, vol. 10, no. 6, pp. 389–402, 2010. View at Publisher · View at Google Scholar · View at Scopus
- Z. Huang, D. Huang, S. Ni, Z. Peng, W. Sheng, and X. Du, “Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer,” International Journal of Cancer, vol. 127, no. 1, pp. 118–126, 2010. View at Publisher · View at Google Scholar · View at Scopus
- B. M. Bolstad, R. A. Irizarry, M. Åstrand, and T. P. Speed, “A comparison of normalization methods for high density oligonucleotide array data based on variance and bias,” Bioinformatics, vol. 19, no. 2, pp. 185–193, 2003. View at Publisher · View at Google Scholar · View at Scopus
- A. Deo, J. Carlsson, and A. Lindlöf, “How to choose a normalization strategy for miRNA quantitative real-time (QPCR) arrays,” Journal of Bioinformatics and Computational Biology, vol. 9, no. 6, pp. 795–812, 2011. View at Publisher · View at Google Scholar
- Y. J. Hua, K. Tu, Z. Y. Tang, Y. X. Li, and H. S. Xiao, “Comparison of normalization methods with microRNA microarray,” Genomics, vol. 92, no. 2, pp. 122–128, 2008. View at Publisher · View at Google Scholar · View at Scopus
- S. Pradervand, J. Weber, J. Thomas et al., “Impact of normalization on miRNA microarray expression profiling,” RNA, vol. 15, no. 3, pp. 493–501, 2009. View at Publisher · View at Google Scholar · View at Scopus
- M. S. Pepe, R. Etzioni, Z. Feng et al., “Phases of biomarker development for early detection of cancer,” Journal of the National Cancer Institute, vol. 93, no. 14, pp. 1054–1061, 2001. View at Scopus
- R. Simon, M. D. Radmacher, K. Dobbin, and L. M. McShane, “Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification,” Journal of the National Cancer Institute, vol. 95, no. 1, pp. 14–18, 2003. View at Scopus