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Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma

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Abstract

Introduction

Nectins are a family of integral protein and immunoglobulin-like cell adhesion molecules involved in the formation of functioning adherence and tight junctions. Aberrant expression is associated with cancer progression, apoptosis and cell proliferation but little is known how these effects change in cell behavior. The objective of this study was to evaluate the serum levels of nectin-2 with regard to diagnostic, predictive and prognostic value in colorectal cancer (CRC) patients.

Materials and methods

One-hundred and forty CRC patients were enrolled in this study. Serum nectin-2 levels were determined by enzyme-linked immunosorbent assay method. Age- and sex-matched 40 healthy controls were included in the analysis.

Results

Median age of patients was 60 years old, range 24–84 years. The localization of tumor in majority of the patients was colon (n = 81, 58 %). Non-metastatic (stage II and III) and metastatic patients’ baseline serum nectin-2 levels were significantly higher than those in the healthy control group (p < 0.001; for two group). However, known clinical variables including response to CTx (chemotherapy) were not found to be correlated with serum nectin-2 concentrations (p > 0.05). While non-metastatic group patients with elevated serum nectin-2 levels showed significant adverse effect on PFS, metastatic group patients with elevated serum nectin-2 levels showed no significant adverse effect on PFS (p = 0.05 and p = 0.29, respectively). On the other hand, our study results did not show statistically significant serum nectin-2 concentrations regarding overall survival rates.

Conclusion

Serum levels of nectin-2 may have diagnostic roles for CRC patients. Moreover, our study results show the prognostic role of nectin-2 in non-metastatic group patients.

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References

  1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64:104–17.

    Article  PubMed  Google Scholar 

  2. Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.

    Article  PubMed  Google Scholar 

  3. Price TJ, Segelov E, Burge M, Haller DG, Ackland SP, Tebbutt NC, et al. Current opinion on optimal treatment for colorectal cancer. Expert Rev Anticancer Ther. 2013;13:597–611.

    Article  CAS  PubMed  Google Scholar 

  4. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ren F, Wang L, Shen X, Xiao X, Liu Z, Wei P, et al. MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer. Am J Cancer Res. 2015;5(4):1542–52.

    PubMed Central  PubMed  Google Scholar 

  6. Su CY, Lin TC, Lin YF, Chen MH, Lee CH, Wang HY, et al. DDX3 as a strongest prognosis marker and its downregulation promotes metastasis in colorectal cancer. Oncotarget. 2015 [Epub ahead of print].

  7. Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, et al. The preoperative platelet to lymphocyte ratio is a prognostic marker in patients with stage II colorectal cancer. Int J Colorectal Dis. 2015 [Epub ahead of print].

  8. Chen YT, Tsao SC, Yuan SS, Tsai HP, Chai CY. Serine protease ınhibitor Kazal type 1 (SPINK1) promotes proliferation of colorectal cancer through the epidermal growth factor as a prognostic marker. Pathol Oncol Res. 2015 [Epub ahead of print].

  9. Hu Y, Yi B, He S, Liu P, Wang L, Yu J, et al. Clinical significance of miR-1826 as a novel prognostic biomarker in colorectal cancer. Anticancer Agents Med Chem. 2015 [Epub ahead of print].

  10. Kahlert C, Lerbs T, Pecqueux M, Herpel E, Hoffmeister M, Jansen L, et al. Overexpression of SIX1 is an independent prognostic marker in stage I–III colorectal cancer. Int J Cancer. 2015. doi:10.1002/ijc.29596.

    Google Scholar 

  11. Liu G, Zhu J, Yu M, Cai C, Zhou Y, Yu M, et al. Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients. J Transl Med. 2015;13:144.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Koch C, Trojan J. Established and potential predictive biomarkers in gastrointestinal cancer-c-Kit, Her2, Ras and Beyond. Digestion. 2015;91(4):294–302.

    Article  CAS  PubMed  Google Scholar 

  13. Sakisaka T, Takai Y. Biology and pathology of nectins and nectin-like molecules. Curr Opin Cell Biol. 2004;16:513–21.

    Article  CAS  PubMed  Google Scholar 

  14. Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y. The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol. 2007;19:593–602.

    Article  CAS  PubMed  Google Scholar 

  15. Yasumi M, Shimizu K, Honda T, Takeuchi M, Takai Y. Role of each immunoglobulin-like loop of nectin for its cellcell adhesion activity. Biochem Biophys Res Commun. 2003;302:61–6.

    Article  CAS  PubMed  Google Scholar 

  16. Yamada A, Fujita N, Sato T, Okamoto R, Ooshio T, Hirota T, et al. Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells. Oncogene. 2006;25:5085–102.

    Article  CAS  PubMed  Google Scholar 

  17. Takai Y, Nakanishi H. Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci. 2003;116:17–27.

    Article  CAS  PubMed  Google Scholar 

  18. Fukuhara A, Irie K, Yamada A, Katata T, Honda T, Shimizu K, et al. Role of nectin in organization of tight junctions in epithelial cells. Genes Cells. 2002;7:1059–72.

    Article  CAS  PubMed  Google Scholar 

  19. Fukuhara A, Irie K, Nakanishi H, Takekuni K, Kawakatsu T, Ikeda W, et al. Involvement of nectin in the localization of junctional adhesion molecule at tight junctions. Oncogene. 2002;21:7642–55.

    Article  CAS  PubMed  Google Scholar 

  20. Fukuhara A, Shimizu K, Kawakatsu T, Fukuhara T, Takai Y. Involvement of nectin-activated Cdc42 small G protein in organization of adherens and tight junctions in Madin–Darby canine kidney cells. J Biol Chem. 2003;278:51885–93.

    Article  CAS  PubMed  Google Scholar 

  21. Morita H, Nandadasa S, Yamamoto TS, Terasaka-Iioka C, Wylie C, Ueno N. Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis. Development. 2010;137:1315–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Matsushima H, Utani A, Endo H, Matsuura H, Kakuta M, Nakamura Y, et al. The expression of nectin-1alpha in normal human skin and various skin tumours. Br J Dermatol. 2003;148:755–62.

    Article  CAS  PubMed  Google Scholar 

  23. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  24. Malafosse R, Penna C, Sa Cunha A, Nordlinger B. Surgical management of hepatic metastases from colorectal malignancies. Ann Oncol. 2001;12:887–94.

    Article  CAS  PubMed  Google Scholar 

  25. Aslam MI, Taylor K, Pringle JH, Jameson JS. MicroRNAs are novel biomarkers of colorectal cancer. Br J Surg. 2009;96:702–10.

    Article  CAS  PubMed  Google Scholar 

  26. Miyoshi J, Takai Y. Nectin and nectin-like molecules: biology and pathology. Am J Nephrol. 2007;27:590–604.

    Article  CAS  PubMed  Google Scholar 

  27. Takai Y, Miyoshi J, Ikeda W, Ogita H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat Rev Mol Cell Biol. 2008;9:603–15.

    Article  CAS  PubMed  Google Scholar 

  28. Martin TA, Lane J, Harrison GM, Jiang WG. The expression of the Nectin complex in human breast cancer and the role of Nectin-3 in the control of tight junctions during metastasis. PLoS ONE. 2013;8:e82696.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Pende D, Spaggiari GM, Marcenaro S, Martini S, Rivera P, Capobianco A, et al. Analysis of the receptor ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112). Blood. 2005;105:2066–73.

    Article  CAS  PubMed  Google Scholar 

  30. Sanchez-Correa B, Gayoso I, Bergua JM, Casado JG, Morgado S, Solana R, et al. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol Cell Biol. 2012;90:109–15.

    Article  CAS  PubMed  Google Scholar 

  31. El-Sherbiny YM, Meade JL, Holmes TD, McGonagle D, Mackie SL, Morgan AW, et al. The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Res. 2007;67:8444–9.

    Article  CAS  PubMed  Google Scholar 

  32. Oshima T, Sato S, Kato J, Ito Y, Watanabe T, Tsuji I, et al. Nectin-2 is potential target for antibody therapy of breast and ovarian cancers. Mol Cancer. 2013;12:60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Miao X, Yang ZL, Xiong L, Zou Q, Yuan Y, Li J, et al. Nectin-2 and DDX3 are biomarkers for metastasis and poor prognosis of squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder. Int J Clin Exp Pathol. 2013;6:179–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Raveh S, Gavert N, Spiegel I, Ben-Ze’ev A. The cell adhesion nectin-like molecules (Necl) 1 and 4 suppress the growth and tumorigenic ability of colon cancer cells. J Cell Biochem. 2009;108(1):326–36.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to C. U. Afsar.

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The authors declare that they have no conflict of interest relating to the publication of this manuscript.

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

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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.

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Karabulut, M., Gunaldi, M., Alis, H. et al. Serum nectin-2 levels are diagnostic and prognostic in patients with colorectal carcinoma. Clin Transl Oncol 18, 160–171 (2016). https://doi.org/10.1007/s12094-015-1348-1

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  • DOI: https://doi.org/10.1007/s12094-015-1348-1

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