Skip to main content

Advertisement

Log in

Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann–Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. DeSantis C, Siegel R, Bandi P, Jemal A (2011) Breast cancer statistics, 2011. CA Cancer J Clin 61:409–418

    Article  PubMed  Google Scholar 

  3. Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW (2003) Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 361:1405–1410

    Article  PubMed  Google Scholar 

  4. Elmore JG, Armstrong K, Lehman CD, Fletcher SW (2005) Screening for breast cancer. JAMA 293:1245–1256

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Cheung KL, Graves CR, Robertson JF (2000) Tumour marker measurements in the diagnosis and monitoring of breast cancer. Cancer Treat Rev 26:91–102

    Article  CAS  PubMed  Google Scholar 

  6. Park BW, Oh JW, Kim JH, Park SH, Kim KS, Lee KS (2008) Preoperative CA15-3 and CEA serum levels as predictor for breast cancer outcomes. Ann Oncol 19:675–681

    Article  PubMed  Google Scholar 

  7. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  8. Bushati N, Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23:175–205

    Article  CAS  PubMed  Google Scholar 

  9. Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596

    Article  CAS  PubMed  Google Scholar 

  10. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  PubMed  Google Scholar 

  11. Du T, Zamore PD (2005) microPrimer: the biogenesis and function of microRNA. Development 132:4645–4652

    Article  CAS  PubMed  Google Scholar 

  12. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826

    Article  CAS  PubMed  Google Scholar 

  13. Miska EA (2005) How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 15:563–568

    Article  CAS  PubMed  Google Scholar 

  14. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  15. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13

    Article  PubMed Central  PubMed  Google Scholar 

  16. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  CAS  PubMed  Google Scholar 

  17. 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 (2008) Serum microRNAs are promising novel biomarkers. PLoS ONE 3:e3148

    Article  PubMed Central  PubMed  Google Scholar 

  18. Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, Poon TC, Ng SS, Sung JJ (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58:1375–1381

    Article  CAS  PubMed  Google Scholar 

  19. Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu ZY, Hood LE, Galas DJ (2009) Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 106:4402–4407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW, Lo YM (2008) Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 54:482–490

    Article  CAS  PubMed  Google Scholar 

  21. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, PogosovaAgadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Chen X, Ba Y, Ma LJ, Cai X, Yin Y, Wang KH, Guo J, Zhang YJ, Chen JN, Guo X, Li QB, Li XY, Wang WJ, Zhang Y, Wang J, Jiang XY, Xiang Y, Xu C, Zheng PP, Zhang JB, Li RQ, Zhang HJ, Shang XB, Gong T, Ning G, Wang J, Zen K, Zhang JF, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006

    Article  CAS  PubMed  Google Scholar 

  23. Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127:118–126

    Article  CAS  PubMed  Google Scholar 

  24. Heneghan HM, Miller N, Kelly R, Newell J, Kerin MJ (2010) Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist 15:673–682

    Article  PubMed Central  PubMed  Google Scholar 

  25. Wang X, Wang J, Ma H, Zhang J, Zhou X (2012) Downregulation of miR-195 correlates with lymph node metastasis and poor prognosis in colorectal cancer. Med Oncol 29:919–927

  26. Xu T, Zhu Y, Xiong Y, Ge YY, Yun JP, Zhuang SM (2009) MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 50:113–121

    Article  CAS  PubMed  Google Scholar 

  27. Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu C-G, Calin GA, Giovannini C, Ferrazzi E, Grazi GL, Croce CM, Bolondi L, Negrini M (2007) Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 67:6092–6099

    Article  CAS  PubMed  Google Scholar 

  28. Sekiya Y, Ogawa T, Iizuka M, Yoshizato K, Ikeda K, Kawada N (2011) Down-regulation of cyclin E1 expression by MicroRNA-195 accounts for interferon-β-induced inhibition of hepatic stellate cell proliferation. J Cell Physiol 226:2535–2542

    Article  CAS  PubMed  Google Scholar 

  29. Ichimi T, Enokida H (2009) Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer 125:345–352

    Article  CAS  PubMed  Google Scholar 

  30. Han Y, Chen J, Zhao X, Liang C, Wang Y, Sun L, Jiang Z, Zhang Z, Yang R, Chen J, Li Z, Tang A, Li X, Ye J, Guan Z, Gui Y, Cai Z (2011) MicroRNA expression signatures of bladder cancer revealed by deep sequencing. PLoS ONE 6:e18286

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, Fujimura L, Kikkawa N, Seki N, Nakagawa M (2010) iR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer 102:883–891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D, Wang Y (2009) Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol 24:652–657

    Article  CAS  PubMed  Google Scholar 

  33. Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI (2008) Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res 14:2588–2592

    Article  CAS  PubMed  Google Scholar 

  34. Hannafon BN, Sebastiani P, de Las Morenas A, Lu J, Rosenberg CL (2011) Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res 13:R24

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67:8699–8707

    Article  CAS  PubMed  Google Scholar 

  36. Flavin RJ, Smyth PC, Laios A, O’Toole SA, Barrett C, Finn SP, Russell S, Ring M, Denning KM, Li J (2009) Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma. Mod Pathol 22:197–205. doi:10.1038/modpathol.2008.135

    Article  CAS  PubMed  Google Scholar 

  37. Soon PS, Tacon LJ, Gill AJ, Bambach CP, Sywak MS, Campbell PR, Yeh MW, Wong SG, Clifton-Bligh RJ, Robinson BG, Sidhu SB (2009) miR-195 and miR-483–5p identified as predictors of poor prognosis in adrenocortical cancer. Clin Cancer Res 15:7684–7692

    Article  CAS  PubMed  Google Scholar 

  38. Li D, Zhao Y, Liu C, Chen X, Qi Y, Jiang Y, Zou C, Zhang X, Liu S, Wang X, Zhao D, Sun Q, Zeng Z, Dress A, Lin MC, Kung HF, Rui H, Liu LZ, Mao F, Jiang BH, Lai L (2011) Analysis of MiR-195 and MiR-497 expression, regulation and role in breast cancer. Clin Cancer Res 17:1722–1730

    Article  CAS  PubMed  Google Scholar 

  39. Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S (2010) A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS ONE 5:e13735

    Article  PubMed Central  PubMed  Google Scholar 

  40. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101:2999–3004

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Staub E, Gröne J, Mennerich D, Röpcke S, Klamann I, Hinzmann B, Castanos VE, Mann B, Pilarsky C, Brümmendorf T, Weber B, Buhr HJ, Rosenthal A (2006) A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer. Mol Cancer 5:37

    Article  PubMed Central  PubMed  Google Scholar 

  42. Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, Kuroda M (2009) Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS ONE 4:e5532

    Article  PubMed Central  PubMed  Google Scholar 

  43. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, Sen S (2009) MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa) 2:807–813

    Article  CAS  Google Scholar 

  44. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE (2009) The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 112:55–59

    Article  CAS  PubMed  Google Scholar 

  45. Liu Q, Fu H, Sun F, Zhang H, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 36:5391–5404

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Rao X, Di Leva G, Li M, Fang F, Devlin C, Hartman-Frey C, Burow ME, Ivan M, Croce CM, Nephew KP (2011) MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene 30:1082–1097

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Liu L, Chen L, Xu Y, Li R, Du X (2011) microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells. Biochem Biophys Res Commun 400:236–240

    Article  Google Scholar 

  48. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T (2006) Involvement of human microRNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 130:2113–2129

    Article  CAS  PubMed  Google Scholar 

  50. Weidhaas JB, Babar I, Nallur SM, Trang P, Roush S, Boehm M, Gillespie E, Slack FJ (2007) MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res 67:11111–11116

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ya-kui Zhang.

Additional information

Yue-chao Dou and Fu-long Zhao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Fl., Dou, Yc., Wang, Xf. et al. Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer. Mol Biol Rep 41, 5913–5922 (2014). https://doi.org/10.1007/s11033-014-3466-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3466-1

Keywords

Navigation