Skip to main content
Log in

Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Purpose

To determine the sensitivity and specificity of serum Cyr61 as a potential biomarker for the diagnosis of colorectal cancer (CRC) and to assess the association between serum Cyr61 level and CRC clinicopathological status.

Methods

We used an enzyme-linked immunosorbent assay to measure serum Cyr61 in patients with CRC, patients with colorectal adenomas, and healthy controls. We also analyzed the relationship between serum Cyr61 and clinicopathological features of CRC patients. The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were quantified using the Roche Cobas 6000 Analyzer. The sensitivity and specificity of Cyr61, CEA, CA19-9 and CEA + CA19-9 were evaluated by receiver operating characteristic (ROC) analysis.

Results

The serum level of Cyr61 was significantly increased in CRC patients compared with colorectal adenoma patients and healthy controls (p < 0.001). Furthermore, the area under the ROC curve for Cyr61 was 0.935 (95 % confidence interval 0.902–0.968), higher than that for CEA + CA19-9 (0.827, 95 % confidence interval: 0.783–0.871). Use of a Cyr61 cutoff value of 92.0 pg/mL allowed distinguishing CRC patients and healthy controls with a sensitivity of 83 % and a specificity of 97 %. Among CRC patients, an elevated level of serum Cyr61 was significantly associated with more advanced TNM stage (p < 0.0042), lymph node metastasis (p < 0.0088), and vascular invasion (p = 0.0027).

Conclusion

Cyr61 has potential as a serum biomarker for the diagnosis of CRC and for assessment of the clinicopathological status of CRC.

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

Similar content being viewed by others

References

  1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104–17. doi:10.3322/caac.21220.

    Article  PubMed  Google Scholar 

  2. Liu S, Zheng R, Zhang M, Zhang S, Sun X, Chen W. Incidence and mortality of colorectal cancer in China, 2011. Chin J Cancer Res. 2015;27(1):22–8. doi:10.3978/j.issn.1000-9604.2015.02.01.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Yoruker EE, Holdenrieder S, Gezer U. Blood-based biomarkers for diagnosis, prognosis and treatment of colorectal cancer. Clin Chim Acta. 2016;455:26–32. doi:10.1016/j.cca.2016.01.016.

    Article  CAS  PubMed  Google Scholar 

  4. Phua LC, Chue XP, Koh PK, Cheah PY, Ho HK, Chan EC. Non-invasive fecal metabonomic detection of colorectal cancer. Cancer Biol Ther. 2014;15(4):389–97. doi:10.4161/cbt.27625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Newton KF, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis. 2012;14(1):3–17. doi:10.1111/j.1463-1318.2010.02439.x.

    Article  CAS  PubMed  Google Scholar 

  6. Chen Y, Du XY. Functional properties and intracellular signaling of CCN1/Cyr61. J Cell Biochem. 2007;100(6):1337–45. doi:10.1002/jcb.21194.

    Article  CAS  PubMed  Google Scholar 

  7. Xie D, Miller CW, O’Kelly J, Nakachi K, Sakashita A, Said JW, et al. Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with more advanced disease. J Biol Chem. 2001;276(17):14187–94. doi:10.1074/jbc.M009755200.

    CAS  PubMed  Google Scholar 

  8. O’Kelly J, Chung A, Lemp N, Chumakova K, Yin D, Wang HJ, et al. Functional domains of CCN1 (Cyr61) regulate breast cancer progression. Int J Oncol. 2008;33(1):59–67.

    PubMed  Google Scholar 

  9. D’Antonio KB, Toubaji A, Albadine R, Mondul AM, Platz EA, Netto GJ, et al. Extracellular matrix associated protein CYR61 is linked to prostate cancer development. J Urol. 2010;183(4):1604–10. doi:10.1016/j.juro.2009.12.006.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Terada N, Kulkarni P, Getzenberg RH. Cyr61 is a potential prognostic marker for prostate cancer. Asian J Androl. 2012;14(3):405–8. doi:10.1038/aja.2011.149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao ZS, Li L, Wang HJ, Wang YY. Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer. J Surg Oncol. 2011;104(5):525–9. doi:10.1002/jso.21984.

    Article  CAS  PubMed  Google Scholar 

  12. Kok SH, Chang HH, Tsai JY, Hung HC, Lin CY, Chiang CP, et al. Expression of Cyr61 (CCN1) in human oral squamous cell carcinoma: an independent marker for poor prognosis. Head Neck. 2010;32(12):1665–73. doi:10.1002/hed.21381.

    Article  PubMed  Google Scholar 

  13. Feng P, Wang B, Ren EC. Cyr61/CCN1 is a tumor suppressor in human hepatocellular carcinoma and involved in DNA damage response. Int J Biochem Cell Biol. 2008;40(1):98–109. doi:10.1016/j.biocel.2007.06.020.

    Article  CAS  PubMed  Google Scholar 

  14. Jeong D, Heo S, Sung Ahn T, Lee S, Park S, Kim H, et al. Cyr61 expression is associated with prognosis in patients with colorectal cancer. BMC Cancer. 2014;14:164. doi:10.1186/1471-2407-14-164.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ladwa R, Pringle H, Kumar R, West K. Expression of CTGF and Cyr61 in colorectal cancer. J Clin Pathol. 2011;64(1):58–64. doi:10.1136/jcp.2010.082768.

    Article  CAS  PubMed  Google Scholar 

  16. Chen VW, Hsieh MC, Charlton ME, Ruiz BA, Karlitz J, Altekruse SF, et al. Analysis of stage and clinical/prognostic factors for colon and rectal cancer from SEER registries: AJCC and collaborative stage data collection system. Cancer. 2014;120(Suppl 23):3793–806. doi:10.1002/cncr.29056.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tsai MS, Bogart DF, Li P, Mehmi I, Lupu R. Expression and regulation of Cyr61 in human breast cancer cell lines. Oncogene. 2002;21(6):964–73. doi:10.1038/sj.onc.1205131.

    Article  CAS  PubMed  Google Scholar 

  18. Bleau AM, Planque N, Perbal B. CCN proteins and cancer: two to tango. Front Biosci. 2005;10:998–1009.

    Article  CAS  PubMed  Google Scholar 

  19. Li J, Ye L, Owen S, Weeks HP, Zhang Z, Jiang WG. Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (review). Int J Mol Med. 2015;36(6):1451–63. doi:10.3892/ijmm.2015.2390.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Shah R, Jones E, Vidart V, Kuppen PJ, Conti JA, Francis NK. Biomarkers for early detection of colorectal cancer and polyps: systematic review. Cancer Epidemiol Biomark Prev. 2014;23(9):1712–28. doi:10.1158/1055-9965.EPI-14-0412.

    Article  CAS  Google Scholar 

  21. Booth RA. Minimally invasive biomarkers for detection and staging of colorectal cancer. Cancer Lett. 2007;249(1):87–96. doi:10.1016/j.canlet.2006.12.021.

    Article  CAS  PubMed  Google Scholar 

  22. Obrocea FL, Sajin M, Marinescu EC, Stoica D. Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting. Rom J Morphol Embryol. 2011;52(2):537–44.

    CAS  PubMed  Google Scholar 

  23. Jiang WG, Watkins G, Fodstad O, Douglas-Jones A, Mokbel K, Mansel RE. Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer. Endocr Relat Cancer. 2004;11(4):781–91. doi:10.1677/erc.1.00825.

    Article  CAS  PubMed  Google Scholar 

  24. Schmitz P, Gerber U, Jungel E, Schutze N, Blaheta R, Bendas G. Cyr61/CCN1 affects the integrin-mediated migration of prostate cancer cells (PC-3) in vitro. Int J Clin Pharmacol Ther. 2013;51(1):47–50.

    Article  PubMed  Google Scholar 

  25. Lin J, Huo R, Wang L, Zhou Z, Sun Y, Shen B, et al. A novel anti-Cyr61 antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol Immunother. 2012;61(5):677–87. doi:10.1007/s00262-011-1135-y.

    Article  CAS  PubMed  Google Scholar 

  26. Lin MT, Zuon CY, Chang CC, Chen ST, Chen CP, Lin BR, et al. Cyr61 induces gastric cancer cell motility/invasion via activation of the integrin/nuclear factor-kappaB/cyclooxygenase-2 signaling pathway. Clin Cancer Res. 2005;11(16):5809–20. doi:10.1158/1078-0432.CCR-04-2639.

    Article  CAS  PubMed  Google Scholar 

  27. Fujii T, Sutoh T, Morita H, Yajima R, Yamaguchi S, Tsutsumi S, et al. Vascular invasion, but not lymphatic invasion, of the primary tumor is a strong prognostic factor in patients with colorectal cancer. Anticancer Res. 2014;34(6):3147–51.

    PubMed  Google Scholar 

  28. Naito Y, Goto K, Nagai K, Ishii G, Nishimura M, Yoshida J, et al. Vascular invasion is a strong prognostic factor after complete resection of node-negative non-small cell lung cancer. Chest. 2010;138(6):1411–7. doi:10.1378/chest.10-0185.

    Article  PubMed  Google Scholar 

  29. Betge J, Langner C. Vascular invasion, perineural invasion, and tumour budding: predictors of outcome in colorectal cancer. Acta Gastroenterol Belg. 2011;74(4):516–29.

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Natural Science Foundation of Fujian Province (2015J01400, 2016J01569).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to B. Song or Q. Lin.

Ethics declarations

Conflict of interest

There are no conflicts of interest to declare.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Y. F. Song and Z. B. Xu contributed equally to this work.

B. Song and Q. Lin both corresponding authors 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

Song, Y.F., Xu, Z.B., Zhu, X.J. et al. Serum Cyr61 as a potential biomarker for diagnosis of colorectal cancer. Clin Transl Oncol 19, 519–524 (2017). https://doi.org/10.1007/s12094-016-1560-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-016-1560-7

Keywords

Navigation