Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients

  • Cecener, Gulsah (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Ak, Secil (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Eskiler, Gamze Guney (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Demirdogen, Elif (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Erturk, Elif (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Gokgoz, Sehsuvar (Department of General Surgery, Medical Faculty, Uludag University) ;
  • Polatkan, Volkan (Department of General Surgery, Medical Faculty, Uludag University) ;
  • Egeli, Unal (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Tunca, Berrin (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Tezcan, Gulcin (Department of Medical Biology, Medical Faculty, Uludag University) ;
  • Topal, Ugur (Department of Radiology, Medical Faculty, Uludag University) ;
  • Tolunay, Sahsine (Department of Pathology, Medical Faculty, Uludag University) ;
  • Tasdelen, Ismet (Department of General Surgery, Medical Faculty, Uludag University)
  • Published : 2016.09.01
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Abstract

Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre- and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p=0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

Keywords

Acknowledgement

Supported by : Uludag University of Turkey

References

  1. Allegra A, Alonci A, Campo S, et al (2012). Circulating microRNA: New biomarkers in diagnosis, prognosis and treatment of cancer. Int J Oncol, 41, 1897-912. https://doi.org/10.3892/ijo.2012.1647
  2. Aquilar F, Ramirez JA, Malagon-Santiago I, et al (2013). Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Disease Markers, 34, 163-169. https://doi.org/10.1155/2013/259454
  3. Asaga S, Kuo C, Nguyen T, et al (2011). Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem, 57, 84-91. https://doi.org/10.1373/clinchem.2010.151845
  4. Calin GA, Croce CM, (2006). MicroRNA signatures in human cancers. Nature Reviews Cancer, 6, 857-66. https://doi.org/10.1038/nrc1997
  5. Chan M, Liaw CS, Ji SM, (2013). Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res, 19, 4477-87. https://doi.org/10.1158/1078-0432.CCR-12-3401
  6. Chen G, Wang J, Cui Q, (2013). Could circulating miRNAs contribute to cancer therapy? Trends Mol Med, 19, 71-3. https://doi.org/10.1016/j.molmed.2012.10.006
  7. Corcoran C, Friel AM, Duffy MJ, et al (2011). Intracellular and extracellular MicroRNAs in breast cancer. Clin Chem, 57, 18-32. https://doi.org/10.1373/clinchem.2010.150730
  8. Cortez MA, Welsh JW, Calin GA, (2012). Circulating microRNAs as noninvasive biomarkers in breast cancer. Recent Results Cancer Res, 195, 151-61.
  9. Creighton CJ, (2012). The molecular profile of luminal B breast cancer. Biologics: Targets Therapy, 6, 289-97.
  10. Cuk K, Zucknick M, Heil J, et al (2013). Circulating micrornas in plasma as early detection markers for breast cancer. Int J Cancer, 132, 1602-12. https://doi.org/10.1002/ijc.27799
  11. Demirdogen Sevinc E, Egeli U, Cecener G, et al (2015). Association of miR-1266 with Recurrence/Metastasis Potential in Estrogen Receptor Positive Breast Cancer. Asian Pac J Cancer Prev, 16, 291-7 https://doi.org/10.7314/APJCP.2015.16.1.291
  12. Desantis C, Ma J, Bryan L, et al (2014). Breast cancer statistics. CA Cancer J Clin, 64, 52-62. https://doi.org/10.3322/caac.21203
  13. EK Ng, Li R, Shin VY, et al (2013). Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One, 8, 531-41.
  14. Erturk E, Cecener G, Egeli U, et al (2014). Expression status of let-7a and miR-335 among breast tumors in patients with and without germ-line BRCA mutations. Mol Cell Biochem, 395, 77-88. https://doi.org/10.1007/s11010-014-2113-4
  15. Filipowicz W, Bhattacharyya SN, Sonenberg N, (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics, 9, 102-14. https://doi.org/10.1038/nrg2290
  16. He L, Hannon GJ (2004). MicroRNAs: Small RNAs with a big role in gene regulation. Nature Rev Genet, 5, 522-31. https://doi.org/10.1038/nrg1379
  17. Heneghan HM, Miller N, Kelly R, et al (2010). Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist, 15, 673-82. https://doi.org/10.1634/theoncologist.2010-0103
  18. Heneghan HM, Miller N, Kerin MJ, (2011). Circulating microRNAs: promising breast cancer biomarkers. Breast Cancer Res, 13, 402. https://doi.org/10.1186/bcr2798
  19. Heneghan HM, Miller N, Lowery AJ, et al (2010). Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg, 251, 499-505. https://doi.org/10.1097/SLA.0b013e3181cc939f
  20. Iorio MV, Casalini P, Tagliabue E, et al (2008). MicroRNA profiling as a tool to understand prognosis, therapy response and resistance in breast cancer. European J Cancer, 44, 2753-9. https://doi.org/10.1016/j.ejca.2008.09.037
  21. Iorio MV, Ferracin M, Liu CG, (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res, 65, 7065-70. https://doi.org/10.1158/0008-5472.CAN-05-1783
  22. Jack RH, Davies EA, Renshaw C, et al (2013). Differences in breast cancer hormone receptor status in ethnic groups: A London population. Eur J Cancer, 49, 696-702. https://doi.org/10.1016/j.ejca.2012.09.012
  23. Kavitha N, Vijayarathna S, Jothy SL, et al (2014). MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis. Asian Pac J Cancer Prev, 15, 7489-97. https://doi.org/10.7314/APJCP.2014.15.18.7489
  24. Kayani MR, Kayani MA, Malik FA et al (2011). Role of miRNAs in breast cancer. Asian Pacific J Cancer Prev, 12, 3175-80.
  25. Kosaka N, Iguchi H, Ochiya T, (2010). Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci, 101, 2087-92. https://doi.org/10.1111/j.1349-7006.2010.01650.x
  26. Livak KJ, Schmittgen T.D, (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2- ${\Delta}{\Delta}CT$) method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  27. Lowery AJ, Miller N, McNeill RE, et al (2008). MicroRNAs as prognostic indicators and therapeutic targets: potential effect on breast cancer management. Clin Cancer Res, 14, 360-5. https://doi.org/10.1158/1078-0432.CCR-07-0992
  28. Lu J, Getz G, Miska EA, et al (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834-8. https://doi.org/10.1038/nature03702
  29. Luo Q, Wei C, Li X, et al (2014). MicroRNA-195-5p is a potential diagnostic and therapeutic target for breast cancer. Oncol Reps, 31, 1096-102. https://doi.org/10.3892/or.2014.2971
  30. Ma R, Jiang T, Kang X (2012). Circulating microRNAs in cancer: origin, function and application. JECCR, 31, 38.
  31. Ma R, Jiang T, Kang X (2012). Circulating microRNAs in cancer: origin, function and application. J Exp Clin Can, 31, 38. https://doi.org/10.1186/1756-9966-31-38
  32. Madhavan D, Cuk K, Burwinkel B, et al (2013). Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. FGENE, 4.
  33. Madhavan D, Zucknick M, Wallwiener M, et al (2012). Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res, 18, 5972-82. https://doi.org/10.1158/1078-0432.CCR-12-1407
  34. Mirnezami AH, Pickard K, Zhang L, et al (2009). MicroRNAs: key players in carcinogenesis and novel therapeutic targets. Eur J Surg Oncol, 3, 339-47.
  35. Qu H, Xu W , Huang Y et al (2011). Circulating miRNAs: promising biomarkers of human cancer. Asian Pac J Cancer Prev, 12, 1117-25.
  36. Roth C, Rack B, Muller V, et al (2010). Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res, 12.
  37. Roth C, Rack B, Muller V, et al (2010). Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res, 12, 90. https://doi.org/10.1186/bcr2766
  38. Sarfati D, Blakely T, Shaw C, et al (2006). Patterns of disparity: ethnic and socio-economic trends in breast cancer mortality in New Zealand. Cancer Causes Control, 17, 671-8. https://doi.org/10.1007/s10552-005-0583-0
  39. Schrauder MG, Strick R, Schulz-Wendtland R, et al (2012). Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One, 7, 1-9.
  40. Shavers VL, Brown ML, (2002). Racial and ethnic disparities in the receipt of cancer treatment. J National Cancer Inst, 94, 334-57. https://doi.org/10.1093/jnci/94.5.334
  41. Shavers VL, Brown M.L, (2002). Racial and ethnic disparities in the receipt of cancer treatment. J National Cancer Inst, 94, 334-57. https://doi.org/10.1093/jnci/94.5.334
  42. Shen J, Ambrosone CB, DiCioccio RA, et al (2008). A functional polymorphism in the miR-146a gene and age of familialbreast/ovarian cancer diagnosis. Carcinogenesis, 29, 1963-66. https://doi.org/10.1093/carcin/bgn172
  43. Si H, Sun X, Chen Y, et al (2013). Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol, 139, 223-9. https://doi.org/10.1007/s00432-012-1315-y
  44. Sun Y, Wang M, Lin G, et al (2012). Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One, 7.
  45. Uchida N, Suda T, et al (2013). Effect of chemotherapy for Luminal A breast cancer. Acta Med, 56, 51-6.
  46. Vasudevan S, Tong YC, Steitz JA, (2007). Switching from repression to activation: MicroRNAs can up-regulate translation. Sci, 318, 1931-34. https://doi.org/10.1126/science.1149460
  47. Wang H, Tan G, Dong L, et al (2012). Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One, 7.
  48. Wang J, Zhang K, Liu S, et al (2014). Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules, 19, 1912-38. https://doi.org/10.3390/molecules19021912
  49. Wiencke JK (2004). Impact of race/ethnicity on molecular pathways in human cancer. Nat Rev Cancer, 4, 79-84. https://doi.org/10.1038/nrc1257
  50. Wu Q, Lu Z, Li H, et al (2011). Next-generation sequencing of microRNAs for breast cancer detection. J Biomed Biotechnol.
  51. Wu X, Somlo G, Yu Y, et al (2012). De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med, 10, 42. https://doi.org/10.1186/1479-5876-10-42
  52. Yanagawa M, Ikemot K, Kawauchi S, et al (2012). Luminal A and Luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotypes. BMC Research Notes, 5, 376. https://doi.org/10.1186/1756-0500-5-376
  53. Zhang H, Su B, Zhou QM, et al (2009). Differential expression