DOI QR코드

DOI QR Code

Characterization of CCND1 and TWIST1 as Prognostic Markers with the Mortality Rate of Breast Cancer

  • Ahn, Sungwoo (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Park, Sangjung (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Wang, Hye-Young (Optipharm M&D, Inc., Wonju Eco Environmental Technology Center) ;
  • Park, Sunyoung (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Jungho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lee, Hyeyoung (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • Received : 2018.05.03
  • Accepted : 2018.06.14
  • Published : 2018.06.30

Abstract

Breast cancer is one of the most common cancers affecting women worldwide. Although the survival rate of breast cancer has increased, breast cancer still results in a high mortality rate. Breast cancer deaths are caused by metastasis that occurs in organ dysfunction. Recently, there have been many studies on circulating tumor cells (CTCs), which are related to breast cancer metastasis in the blood. Recent studies have demonstrated that some CTCs do not express epithelial markers. Therefore, in this study, total RNA was extracted from blood without separating out the CTCs, and the characteristics of the CTCs were analyzed by RT-qPCR. Cyclin D1 and twist-related protein 1 (TWIST1) are well-known markers for predicting the prognosis of patients with breast cancer. However, few studies have demonstrated the use of CCND1 and TWIST1 in blood as diagnostic and prognostic markers of breast cancer. In this study, patients with late-stage breast cancer had overexpressed CCND1 and TWIST1 than patients with different stages of breast cancer (P < 0.001 and P < 0.01, respectively). The relative expression level of CCND1 in survivors was higher than in patients who died (P = 0.06). The relative expression level of TWIST1 in survivors was lower than in patients who died (P = 0.08). Overall CCND1 and TWIST1 were not useful as markers for the diagnosis of breast cancer through blood. However, we showed the possibility of using CCND1 and TWIST1 as prognostic markers, and a large-scale study is needed to confirm the usefulness of these prognostic markers.

Keywords

References

  1. Ansieau S, Morel AP, Hinkal G, Bastid J, Puisieux A. TWISTing an embryonic transcription factor into an oncoprotein. Oncogene. 2010. 29: 3173-3184. https://doi.org/10.1038/onc.2010.92
  2. Barnes DM, Gillett CE. Cyclin D1 in breast cancer. Breast Cancer Research and Treatment. 1998. 52: 1-15. https://doi.org/10.1023/A:1006103831990
  3. Barriere G, Riouallon A, Renaudie J, Tartary M, Rigaud M. Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis. BMC Cancer. 2012. 12: 114-120. https://doi.org/10.1186/1471-2407-12-114
  4. Bonnomet A, Brysse A, Tachsidis A, Waltham M, Thompson EW, Polette M, Gilles C. Epithelial-to-mesenchymal transitions and circulating tumor cells. Journal of Mammary Gland Biology and Neoplasia. 2010. 15: 261-273. https://doi.org/10.1007/s10911-010-9174-0
  5. Bostner J, Ahnstrom Waltersson M, Fornander T, Skoog L, Nordenskjold B, Stal O. Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene. 2007. 26: 6997-7005. https://doi.org/10.1038/sj.onc.1210506
  6. Croset M, Goehrig D, Frackowiak A, Bonnelye E, Ansieau S, Puisieux A, Clezardin P. TWIST1 expression in breast cancer cells facilitates bone metastasis formation. J Bone Miner Res. 2014. 29: 1886-1899. https://doi.org/10.1002/jbmr.2215
  7. Elsheikh S, Green AR, Aleskandarany MA, Grainge M, Paish CE, Lambros MBK, Reis-Filho JS, Ellis IO. CCND1 amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome. Breast Cancer Research and Treatment. 2008. 109: 325-335. https://doi.org/10.1007/s10549-007-9659-8
  8. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015. 136: 359-386. https://doi.org/10.1002/ijc.29210
  9. Hansen NM, Grube B, Ye X, Turner RR, Brenner RJ, Sim MS, Giuliano AE. Impact of micrometastases in the sentinel node of patients with invasive breast cancer. J Clin Oncol. 2009. 27: 4679-4684. https://doi.org/10.1200/JCO.2008.19.0686
  10. Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Priest LJ, Greystoke A, Zhou C, Morris K, Ward T, Blackhall FH, Dive C. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012. 30: 525-532. https://doi.org/10.1200/JCO.2010.33.3716
  11. Jares P, Colomer D, Campo E. Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nat Rev Cancer. 2007. 7: 750-762. https://doi.org/10.1038/nrc2230
  12. Khan MA, Chen HC, Zhang D, Fu J. Twist: a molecular target in cancer therapeutics. Tumor Biology. 2013. 34: 2497-2506. https://doi.org/10.1007/s13277-013-1002-x
  13. Kim MJ, Choi NY, Lee EK, Kang MS. Identification of novel markers that outperform EpCAM in quantifying circulating tumor cells. Cellular Oncology. 2014. 37: 235-243. https://doi.org/10.1007/s13402-014-0178-4
  14. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells-biology and biomarkers. Nat Rev Clin Oncol. 2014. 11: 129-144. https://doi.org/10.1038/nrclinonc.2013.253
  15. Lehn S, Tobin NP, Berglund P, Nilsson K, Sims AH, Jirstrom K, Harkonen P, Lamb R, Landberg G. Down-regulation of the oncogene cyclin D1 increases migratory capacity in breast cancer and is linked to unfavorable prognostic features. Am J Pathol. 2010. 177: 2886-2897. https://doi.org/10.2353/ajpath.2010.100303
  16. Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, Aktas B, Kasimir-Bauer S, Pantel K, Fehm T. Prognostic impact of circulating tumor cells assessed with the CellSearch $System^{TM}$ and AdnaTest $Breast^{TM}$ in metastatic breast cancer patients: the DETECT study. Breast Cancer Research. 2012. 14: R118. https://doi.org/10.1186/bcr3243
  17. Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, Payette T, Pistone M, Stecker K, Zhang BM, Zhou YX, Varnholt H, Smith B, Gadd M, Chatfield E, Kessler J, Baer TM, Erlander MG, Sgroi DC. Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A. 2003. 100: 5974-5979. https://doi.org/10.1073/pnas.0931261100
  18. Markiewicz A, Ksiazkiewicz M, Welnicka-Jaskiewicz M, Seroczynska B, Skokowski J, Szade J, Zaczek AJ. Mesenchymal phenotype of CTC-enriched blood fraction and lymph node metastasis formation potential. PLoS One. 2014. 9:e93901. https://doi.org/10.1371/journal.pone.0093901
  19. Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005. 12:488-496. https://doi.org/10.1245/ASO.2005.04.010
  20. Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R, Jemal A. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016. 66: 271-289. https://doi.org/10.3322/caac.21349
  21. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991. 350: 512-515. https://doi.org/10.1038/350512a0
  22. Oesterreich S, Deng W, Jiang S, Cui X, Ivanova M, Schiff R, Kang K, Hadsell DL, Behrens J, Lee AV. Estrogen-mediated Down-Regulation of E-cadherin in Breast Cancer Cells. J Cancer Research. 2003. 63: 5203-5208.
  23. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2016. 35: 1216-1224. https://doi.org/10.1038/onc.2015.192
  24. Politaki E, Agelaki S, Apostolaki S, Hatzidaki D, Strati A, Koinis F, Perraki M, Saloustrou G, Stoupis G, Kallergi G, Spiliotaki M, Skaltsi T, Lianidou E, Georgoulias V, Mavroudis D. A comparison of three methods for the detection of circulating tumor cells in patients with early and metastatic breast cancer. Cell Physiol Biochem. 2017. 44: 594-606. https://doi.org/10.1159/000485115
  25. Qin Q, Xu Y, He T, Qin C, Xu J. Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res. 2012. 22: 90-106. https://doi.org/10.1038/cr.2011.144
  26. Raimondi C, Gradilone A, Naso G, Cortesi E, Gazzaniga P. Clinical utility of circulating tumor cell counting through CellSearch ((R)): the dilemma of a concept suspended in Limbo. Onco Targets Ther. 2014. 7: 619-625.
  27. Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis. Journal of Internal Medicine. 2013. 274: 113-126. https://doi.org/10.1111/joim.12084
  28. Reis-Filho JS, Savage K, Lambros MB, James M, Steele D, Jones RL, Dowsett M. Cyclin D1 protein overexpression and CCND1 amplification in breast carcinomas: an immunohistochemical and chromogenic in situ hybridisation analysis. Mod Pathol. 2006. 19: 999-1009. https://doi.org/10.1038/modpathol.3800621
  29. Tian X, Aruva MR, Zhang K, Shanthly N, Cardi CA, Thakur ML, Wickstrom E. PET imaging of CCND1 mRNA in human MCF7 estrogen receptor positive breast cancer xenografts with oncogene-specific [64Cu]chelator-peptide nucleic acid-IGF1 analog radiohybridization probes. J Nucl Med. 2007. 48: 1699-1707. https://doi.org/10.2967/jnumed.107.042499
  30. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015. 65: 87-108. https://doi.org/10.3322/caac.21262
  31. Vesuna F, Lisok A, Kimble B, Domek J, Kato Y, van der Groep P, Artemov D, Kowalski J, Carraway H, van Diest P, Raman V. Twist contributes to hormone resistance in breast cancer by downregulating estrogen receptor-alpha. Oncogene. 2012. 31: 3223-3234. https://doi.org/10.1038/onc.2011.483
  32. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004. 117: 927-939. https://doi.org/10.1016/j.cell.2004.06.006
  33. Zhang YQ, Wei XL, Liang YK, Chen WL, Zhang F, Bai JW, Qiu SQ, Du CW, Huang WH, Zhang GJ. Over-expressed twist associates with markers of epithelial mesenchymal transition and predicts poor prognosis in breast cancers via ERK and Akt activation. PLoS One. 2015. 10: e0135851. https://doi.org/10.1371/journal.pone.0135851