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Circulating microRNA 483-5p as a novel biomarker for diagnosis survival prediction in multiple myeloma

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Abstract

Dysregulation of miRNA expression plays an important role in cancer development, and circulating miRNAs are biomarkers of several cancers. We explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma. miRNA microarray was conducted to identify elevation of four miRNAs and reduced levels of eight miRNAs in the plasma of nine multiple myeloma patients and seven healthy controls. Increased miR-483-5p levels and decreased miR-20a were further validated in the plasma of 40 myeloma patients and 20 healthy controls using TaqMan quantitative real-time PCR. Receiver operating characteristic (ROC) analysis revealed that miR-483-5p and miR-20a had considerable diagnostic accuracy, yielding the areas under the ROC curve of 0.745 (sensitivity 58 %, specificity 90 %) and 0.74 (sensitivity 63 %, specificity 85 %), respectively. Plasma levels of miR-483-5p were associated with ISS staging. Within 14 months of diagnosis, the median progression-free survival of patients with high levels of plasma miR-483-5p was 15 months, in comparison with 21 months for patients with low levels of plasma miR-483-5p (p = 0.025). However, miR-20a levels were not correlated with progression-free survival (p > 0.05). miR-483-5p has the potential to be a predictor of myeloma survival.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  2. Corthals SL, Sun SM, Kuiper R, de Knegt Y, Broyl A, van der Holt B, Beverloo HB, Peeters JK, el JL, Lokhorst HM, Zweegman S, Jongen-Lavrencic M, Sonneveld P. MicroRNA signatures characterize multiple myeloma patients. Leukemia. 2011;25:1784-9.

  3. Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K, Radmacher MD, Li C, Whitman SP, Mishra A, Stauffer N, Eiring AM, Briesewitz R, Baiocchi RA, Chan KK, Paschka P, Caligiuri MA, Byrd JC, Croce CM, Bloomfield CD, Perrotti D, Garzon R, Marcucci G. Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia. Cancer Cell. 2010;17:333–47.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087–92.

    Article  PubMed  CAS  Google Scholar 

  5. Li Y, Vecchiarelli-Federico LM, Li YJ, Egan SE, Spaner D, Hough MR, Ben-David Y. The miR-17-92 cluster expands multipotent hematopoietic progenitors whereas imbalanced expression of its individual oncogenic miRNAs promotes leukemia in mice. Blood. 2012;119:4486–98.

    Article  PubMed  CAS  Google Scholar 

  6. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, Zanesi N, Crawford M, Ozer GH, Wernicke D, Alder H, Caligiuri MA, Nana-Sinkam P, Perrotti D, Croce CM. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109:E2110–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Lionetti M, Biasiolo M, Agnelli L, Todoerti K, Mosca L, Fabris S, Sales G, Deliliers GL, Bicciato S, Lombardi L, Bortoluzzi S, Neri A. Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma. Blood. 2009;114:e20–6.

    Article  PubMed  CAS  Google Scholar 

  8. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.

    Article  PubMed  CAS  Google Scholar 

  9. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.

    Article  PubMed  CAS  Google Scholar 

  11. Scholer N, Langer C, Dohner H, Buske C, Kuchenbauer F. Serum microRNAs as a novel class of biomarkers: a comprehensive review of the literature. Exp Hematol. 2010;38:1126–30.

    Article  PubMed  Google Scholar 

  12. Ajit SK. Circulating microRNAs as biomarkers, therapeutic targets, and signaling molecules. Sensors (Basel). 2012;12:3359–69.

    Article  CAS  Google Scholar 

  13. Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One. 2010;5:e13515.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3:e3148.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol. 2009;112:55–9.

    Article  PubMed  CAS  Google Scholar 

  16. Valladares-Ayerbes M, Reboredo M, Medina-Villaamil V, Iglesias-Diaz P, Lorenzo-Patino MJ, Haz M, Santamarina I, Blanco M, Fernandez-Tajes J, Quindos M, Carral A, Figueroa A, Anton-Aparicio LM, Calvo L. Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer. J Transl Med. 2012;10:186.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Tomokuni A, Takemasa I, Umeshita K, Kanto T, Doki Y, Mori M. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75.

    Article  PubMed  CAS  Google Scholar 

  18. Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–93.

    Article  PubMed  CAS  Google Scholar 

  19. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, Li J. Serum MicroRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012;7:e47003.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Fayyad-Kazan H, Bitar N, Najar M, Lewalle P, Fayyad-Kazan M, Badran R, Hamade E, Daher A, Hussein N, ElDirani R, Berri F, Vanhamme L, Burny A, Martiat P, Rouas R, Badran B. Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia. J Transl Med. 2013;11:31.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.

    Article  PubMed  Google Scholar 

  22. Jones CI, Zabolotskaya MV, King AJ, Stewart HJ, Horne GA, Chevassut TJ, Newbury SF. Identification of circulating microRNAs as diagnostic biomarkers for use in multiple myeloma. Br J Cancer. 2012;107:1987–96.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Sevcikova S, Kubiczkova L, Sedlarikova L, Slaby O, Hajek R. Serum miR-29a as a marker of multiple myeloma. Leuk Lymphoma. 2013;54:189–91.

    Article  PubMed  CAS  Google Scholar 

  24. Huang JJ, Yu J, Li JY, Liu YT, Zhong RQ. Circulating microRNA expression is associated with genetic subtype and survival of multiple myeloma. Med Oncol. 2012;29:2402–8.

    Article  PubMed  CAS  Google Scholar 

  25. Oerlemans MI, Mosterd A, Dekker MS, de Vrey EA, van Mil A, Pasterkamp G, Doevendans PA, Hoes AW, Sluijter JP. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO Mol Med. 2012;4:1176–85.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Zile MR, Mehurg SM, Arroyo JE, Stroud RE, DeSantis SM, Spinale FG. Relationship between the temporal profile of plasma microRNA and left ventricular remodeling in patients after myocardial infarction. Circ Cardiovasc Genet. 2011;4:614–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298–301.

    Article  PubMed  CAS  Google Scholar 

  28. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36:842–54.

    Article  PubMed  CAS  Google Scholar 

  29. Greipp PR, San MJ, Durie BG, Crowley JJ, Barlogie B, Blade J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.

    Article  PubMed  Google Scholar 

  30. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, Yoshida K, Sasaki H, Nomura S, Seto Y, Kaminishi M, Calin GA, Croce CM. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11:136–46.

    Article  PubMed  CAS  Google Scholar 

  31. White NM, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM. Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol. 2011;8:75–84.

    Article  PubMed  CAS  Google Scholar 

  32. Reid G, Kirschner MB, van Zandwijk N. Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80:193–208.

    Article  PubMed  Google Scholar 

  33. Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, Melton LJ 3rd, Kumar S, Greipp PR, Clark RJ, Rajkumar SV. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia. 2008;22:1933–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Lima LG, Chammas R, Monteiro RQ, Moreira ME, Barcinski MA. Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett. 2009;283:168–75.

    Article  PubMed  CAS  Google Scholar 

  35. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.

    Article  PubMed  CAS  Google Scholar 

  36. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF, Tewari M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Wang K, Zhang S, Weber J, Baxter D, Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 2010;38:7248–59.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Taylor DD, Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol. 2011;33:441–54.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by National Natural Science Foundation of China (81071946, 81241074, and 81302040); Natural Science Foundation of Jiangsu Province (BK2012485); the Scientific Research Starting Foundation for Returned Overseas Chellonese Scholars, Ministry of Education (2012); Jiangsu Province’s Medical Elite Program (RC201148); “333” project of Jiangsu Province (BRA2011217) and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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The authors have no conflict of interest.

Ethical standards

The study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written informed consent was obtained from all human participants.

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Authors and Affiliations

  1. Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China

    Xiaoyan Qu, Min Zhao, Shuang Wu, Wenjun Yu, Jiaren Xu, Ji Xu, Jianyong Li & Lijuan Chen

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  1. Xiaoyan Qu
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  2. Min Zhao
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Correspondence to Lijuan Chen.

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Xiaoyan Qu and Min Zhao have contributed equally to this work.

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Qu, X., Zhao, M., Wu, S. et al. Circulating microRNA 483-5p as a novel biomarker for diagnosis survival prediction in multiple myeloma. Med Oncol 31, 219 (2014). https://doi.org/10.1007/s12032-014-0219-x

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