Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
권호 표지
DOI QR코드

DOI QR Code

Expression of MicroRNA-221 in Korean Patients with Multiple Myeloma

한국인의 다발성골수종 환자에서 MicroRNA-221의 발현

  • Choi, Woo-Soon (Department of Clinical Laboratory Science, Songho University)
  • 최우순 (송호대학교 임상병리과)
  • Received : 2018.03.23
  • Accepted : 2018.04.26
  • Published : 2018.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Multiple myeloma (MM) is the leading cause of death among hematologic neoplasms. Recently, microRNA has been reported to be useful in the diagnosis of multiple myeloma. This study examined whether miR-221 could be used as a diagnostic marker for multiple myeloma. The study was performed on 20 patients with multiple myeloma without any other hematological diseases. MicroRNA extraction was performed using formalin-fixed paraffin-embedded (FFPE) tissues obtained from the bone marrow of patients with multiple myeloma. miR-15a, miR-16, miR-21, miR-181a, and miR-221 were selected as the microRNA target genes for multiple myeloma. The significance of microRNA was based on a fold change of <1.5. To quantify the fold changes, data normalized to the human gene, SNORD43, were used as the values of the patient group. Fold change values greater than 1.5 were defined as "overexpression", whereas values less than -1.5 were defined as "underexpression". Of note, 65.0% (13/20) of samples showed significant "overexpression" in the levels of miR-221 expression and plasma cells with a group of more and less than 30% in MM patients did not show any significance of plasma cell (P<0.05). The results of other studies showing a correlation between the expression of miR-221 and MM in Caucasians were confirmed. These results suggest that miR-221 may be a useful indicator for diagnosing patients with MM. In conclusion, miR-221 is useful in the diagnosis and determining the prognosis of multiple myeloma in Koreans.

다발성 골수종(MM)은 혈액 종양의 주요 사망 원인이다. 최근에 다발성 골수종 진단에 microRNA를 이용한 실험이 보고되고 있다. 이에 우리는 다발성 골수종 진단 마커로 miR-221을 이용 할 수 있는지 확인하고자 하였다. 본 연구는 다른 혈액학적 질환이 없는 다발성 골수종 환자 20명을 대상으로 하였다. MicroRNA 추출은 다발성 골수종 환자의 파라핀 포매 조직을 이용하였다. 우리는 다발성 골수종의 microRNA 표적 유전자로 miR-15a, miR-16, miR-21, miR-181a 그리고 miR-221을 선택하였다. 유의성 검정은 fold change 값을 기준으로 1.5이상 또는 -1.5 미만의 결과를 유의성이 있는 경우로 하였다. Fold change 값은 인간 유전자 SNORD43에 의해 표준화된 데이터를 기준으로 하였다. Fold change 값이 1.5 이상은 "overexpression", -1.5 미만의 값은 "underexpression"으로 정의되었다. miR-221의 65.0% (13/20)에서 "overexpression"으로 유의성이 있음을 확인하였고, 다발성 골수종 환자에서 형질세포가 30% 이상인 그룹과 이하의 그룹은 유의성을 보이지 않았다. MiR-221은 서구인과 같은 결과를 얻었으며, 다발성 골수종 환자에서 miR-221이 다발성 골수종 환자 진단에 매우 중요한 지표가 될 수 있을 것으로 생각된다. 결론적으로 miR-221은 한국인의 다발성 골수종 진단 또는 예후 지표로 활용할 수 있음을 확인하였다.

Keywords

References

  1. Alexander DD, Mink PJ, Adami HO, Cole P, Mandel JS, Oken MM, et al. Multiple myeloma: a review of the epidemiologic literature. Int J Cancer. 2007;120(Suppl 12):40-61. doi:10.1002/ijc.22718.
  2. Ribatti D, Nico B, Vacca A. Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma. Oncogene. 2006;25:4257-4266. doi:10.1038/sj.onc.1209456.
  3. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420. doi:10.1200/JCO.2005.04.242.
  4. Chng WJ1, Lau LG, Yusof N, Mow BM. Targeted therapy in multiple myeloma. Cancer Control. 2005;12:91-104. doi:https://doi.org/10.1016/ S0037-1963(01)90021-6.
  5. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. 2009;374:324-339. doi: 10.1016/S0140-6736(09)60221-X.
  6. Kumar S. Multiple myeloma-current issues and controversies. Cancer Treat Rev. 2010;36(Suppl 2):3-11. doi:10.1016/S0305-7372(10)70006-2.
  7. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF. et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564-569. doi:10.1146/annurev.arplant.57.032905.105218.
  8. Kyle RA, Therneau TM, Rajkumar SV. Prevalence of monoclonalgammopathy of undetermined significance. N Engl J Med. 2006;354:1362-1369. doi: 10.1056/NEJMoa054494.
  9. Baffa R, Fassan M, Volinia S, O'Hara B, Liu CG, Palazzo JP, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol. 2009;219:214-221. doi:10.1002/path.2586.
  10. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009;137:1005-1017. doi:10.1016/j.cell.2009.04.021.
  11. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425-436. doi:10.1001/jama.299.4.425.
  12. Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 2008;111:3183-3189. doi:10.1182/blood-2007-07-098749.
  13. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130-6135. doi:10.1158/0008-5472.CAN-07-0533.
  14. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer Res. 2007;67:8699-8707. doi:10.1158/0008-5472.CAN-07-1936.
  15. Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006;5:24. doi: 10.1186/1476-4598-5-24.
  16. Roccaro AM, Sacco A, Thompson B, Leleu X, Azab AK, Azab F, et al. MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood. 2009;113:6669-6680. doi:10.1182/blood-2009-01-198408.
  17. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10:704-714. doi: 10.1038/nrg2634.
  18. Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J. The role of microRNAs in normal and malignant hematopoiesis. Eur J Haematol. 2009;84:1-16. doi:10.1111/j.1600-0609.2009.01348.x.
  19. Corthals SL, Jongen-Lavrencic M, de Knegt Y, Peeters JK, Beverloo HB, Lokhorst HM, et al. Micro-RNA-15a and micro-RNA-16 expression and chromosome 13 deletions in multiple myeloma. Leuk Res. 2010;34:677-681. doi:10.1016/j.leukres.2009.10.026.
  20. Kim YK, Yu J, Han TS, Park SY, Namkoong B, Kim DH, et al. Functional links between clustered microRNAs: suppression of cell cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 2009;37:1672-1681. doi:10.1093/nar/gkp002.
  21. Chang HJ, Kim NK, Jeon YJ, Kim JW. The relationship between the progression of colorectal cancer and microRNA polymorphisms. Korean J Clin Oncol. 2011;7:50-57. doi: 10.14216/kjco.11019.
  22. Son JW, Kim YJ, Cho HM, Lee SY, Jang JS, Choi JE, et al. MicroRNA expression profiles Korean non-small cell lung cancer. Tuberc Respir Dis. 2009;67:413-421. doi:https://doi.org/10.4046/trd.2009.67.5.413.
  23. Lee HJ, Park CS, Deftereos G, Morihara J, Stern JE, Hawes SE, et al. MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features. World J Surg Oncol. 2012;10:174. doi:10.1186/1477-7819-10-174.
  24. Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar AK, et al. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediatde induction of microRNA-21 through a highly conserved enhancer. Blood. 2007;110:1330-1333. doi:10.1182/blood-2007-03-081133.
  25. Choi WS, Kwon KC. Expression of microRNA in paraffin embedded tissue of multiple myeloma. Korean J Clin Lab Sci. 2015;47:292-297. doi:https://doi.org/10.15324/kjcls.2015.47.4.292.
  26. Farazi TA, Spitzer JI, Morozov P, Tuschi T. miRNAs in human cancer. J Pathol. 2011;223:102-115. doi:10.1002/path.2806.
  27. Tan KS, Armugam A, Sepramaniam S, Lim KY, Setyowati KD, Wang CW, et al. Expression profile of microRNAs in young stroke patients. PLoS One. 2009;4:e7689. doi:10.1371/journal.pone.0007689.
  28. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:538-548. doi:10.1016/S1470-2045(14)70442-5.
  29. Wu W. MicroRNA: potential targets for the tevelopment of novel drugs?. Drugs R D. 2010;10:1-8. doi:10.2165/11537800-000000000-00000.
  30. Di Martino MT, Gulla A, Gallo Cantafio ME, Altomare E, Amodio N, Leone E, et al. In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells. PLoS One. 2014;9:e89659. doi:10.1371/journal.pone.0089659.
  31. Went P, Mayer S, Oberholzer, Dirnhofer S. Plasma cell quantification in bone marrow by computer-assisted image analysis. Histol Histopathol. 2006;21:951-956. doi: 10.14670/HH-21.951.
  32. Xiang T, Hu AX, Sun P, Liu G, Liu G, Xiao Y. Identification of four potential predicting miRNA biomarkers for multiple myeloma from published datasets. Peer J. 2017;31:e2831. doi:10.7717/peerj.2831.