Skip to main content
SpringerLink
Log in

Synergistic relationship between dipeptidyl peptidase IV and neutral endopeptidase expression and the combined prognostic significance in osteosarcoma patients

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Neutral endopeptidase (NEP/CD10) and dipeptidyl peptidase IV (DPP IV/CD26) are both ubiquitous glycopeptidases which play important roles in tumor pathogenesis and development. The aim of this study was to investigate the expression patterns and the prognostic significance of CD10 and CD26 in osteosarcoma patients. CD10 and CD26 expression in 116 pairs of primary osteosarcoma and corresponding noncancerous bone tissue samples from the same specimens were detected by immunohistochemistry. The Spearman’s correlation was calculated between the expression levels of CD10 and CD26 in osteosarcoma tissues. The associations of CD10 and CD26 expression with the clinicopathologic features and with the prognosis of osteosarcoma were subsequently assessed. Both CD10 expression and CD26 expression in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissue samples (both P < 0.001). Overexpression of CD10 and CD26 were respectively observed in 68.10 % (79/116) and 70.69 % (82/116) of osteosarcoma tissues. A significant correlation was found between CD10 expression and CD26 expression in osteosarcoma tissues (r = 0.83, P < 0.001). In addition, combined overexpression of CD10 and CD26 was observed in 52.59 % (61/116) of osteosarcoma tissues. CD10-high/CD26-high expression was significantly correlated with advanced clinical stage (P = 0.001), positive metastatic status (P = 0.001), shorter overall (P < 0.001) and disease-free (P < 0.001) survival in patients with osteosarcomas. Furthermore, multivariate survival analysis showed that clinical stage, metastatic status, CD10 expression, CD26 expression and combined expression of CD10/CD26 were all independent prognostic factors for predicting both overall and disease-free survival of osteosarcoma patients. Interestingly, combined expression of CD10/CD26 had a better prognostic value than other features. This retrospective study offer the convincing evidence for the first time that the overexpression of CD10 or CD26 may be an important feature of human osteosarcomas, and the combined expression of CD10/CD26 may be an efficient prognostic indicator for this disease.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Selvarajah GT, Kirpensteijn J. Prognostic and predictive biomarkers of canine osteosarcoma. Vet J. 2010;185:28–35.

    Article  PubMed  CAS  Google Scholar 

  2. Lau CC. Molecular classification of osteosarcoma. Cancer Treat Res. 2009;152:459–65.

    Article  PubMed  Google Scholar 

  3. Bakhshi S, Radhakrishnan V. Prognostic markers in osteosarcoma. Expert Rev Anticancer Ther. 2010;10:271–87.

    Article  PubMed  Google Scholar 

  4. Gao Y, Wang J, Fan G. NPRL2 is an independent prognostic factor of osteosarcoma. Cancer Biomark. 2012-2013; 12: 31–6.

    Google Scholar 

  5. Ta HT, Dass CR, Choong PF, Dunstan DE. Osteosarcoma treatment: state of the art. Cancer Metastasis Rev. 2009;28:247–63.

    Article  PubMed  Google Scholar 

  6. Maguer-Satta V, Besançon R, Bachelard-Cascales E. Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells. 2011;29:389–96.

    Article  PubMed  CAS  Google Scholar 

  7. Scholzen TE, Luger TA. Neutral endopeptidase and angiotensin-converting enzyme—key enzymes terminating the action of neuroendocrine mediators. Exp Dermatol. 2004;13:22–6.

    Article  PubMed  CAS  Google Scholar 

  8. Bachelard-Cascales E, Chapellier M, Delay E, et al. The CD10 enzyme is a key player to identify and regulate human mammary stem cells. Stem Cells. 2010;28:1081–8.

    Article  PubMed  CAS  Google Scholar 

  9. Sumitomo M, Shen R, Nanus DM. Involvement of neutral endopeptidase in neoplastic progression. Biochim Biophys Acta. 2005;1751:52–9.

    Article  PubMed  CAS  Google Scholar 

  10. Pilkington GR, Pallesen G. Phenotypic characterization of non-haemopoietic small cell tumours of childhood with monoclonal antibodies to leucocytes, epithelial cells and cytoskeletal proteins. Histopathology. 1989;14:347–57.

    Article  PubMed  CAS  Google Scholar 

  11. Carrel S, Zografos L, Schreyer M, et al. Expression of CALLA/CD10 on human melanoma cells. Melanoma Res. 1993;3:319–23.

    Article  PubMed  CAS  Google Scholar 

  12. Chu P, Arber DA. Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma. Am J Clin Pathol. 2000;113:374–82.

    Article  PubMed  CAS  Google Scholar 

  13. Cohen AJ, Bunn PA, Franklin W, et al. Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux. Cancer Res. 1996;56:831–9.

    PubMed  CAS  Google Scholar 

  14. Yada K, Kashima K, Daa T, et al. Expression of CD10 in basal cell carcinoma. Am J Dermatopathol. 2004;26:463–71.

    Article  PubMed  Google Scholar 

  15. Notohara K, Hamazaki S, Tsukayama C, et al. Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol. 2000;24:1361–71.

    Article  PubMed  CAS  Google Scholar 

  16. Horiguchi A, Chen DY, Goodman OB Jr, et al. Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis. Prostate Cancer Prostatic Dis. 2008;11:79–87.

    Article  PubMed  CAS  Google Scholar 

  17. Borscheri N, Roessner A, Rocken C. Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. Am J Surg Pathol. 2001;25:1297–303.

    Article  PubMed  CAS  Google Scholar 

  18. Makretsov NA, Hayes M, Carter BA, et al. Stromal CD10 expression in invasive breast carcinoma correlates with poor prognosis, estrogen receptor negativity, and high grade. Mod Pathol. 2007;20:84–9.

    Article  PubMed  CAS  Google Scholar 

  19. Huang WB, Zhou XJ, Chen JY, et al. CD10-positive stromal cells in gastric carcinoma: correlation with invasion and metastasis. Jpn J Clin Oncol. 2005;35:245–50.

    Article  PubMed  Google Scholar 

  20. Terauchi M, Kajiyama H, Shibata K, et al. Anti-progressive effect of neutral endopeptidase 24.11 (NEP/CD10) on cervical carcinoma in vitro and in vivo. Oncology. 2005;69:52–62.

    Article  PubMed  CAS  Google Scholar 

  21. Bircan S, Candir O, Kapucuoglu N, et al. CD10 expression in urothelial bladder carcinomas: a pilot study. Urol Int. 2006;77:107–13.

    Article  PubMed  CAS  Google Scholar 

  22. Díaz-Rodríguez L, García-Martínez O, Arroyo-Morales M, Reyes-Botella C, Ruiz C. Antigenic phenotype and phagocytic capacity of MG-63 osteosarcoma line. Ann N Y Acad Sci. 2009;1173:E46–54.

    Article  PubMed  Google Scholar 

  23. Matheeussen V, Jungraithmayr W, De Meester I. Dipeptidyl peptidase 4 as a therapeutic target in ischemia/reperfusion injury. Pharmacol Ther. 2012;136:267–82.

    Article  PubMed  CAS  Google Scholar 

  24. Shipkova M, Wieland E. Surface markers of lymphocyte activation and markers of cell proliferation. Clin Chim Acta. 2012;413:1338–49.

    Article  PubMed  CAS  Google Scholar 

  25. Ohnuma K, Hosono O, Dang NH, Morimoto C. Dipeptidyl peptidase in autoimmune pathophysiology. Adv Clin Chem. 2011;53:51–84.

    Article  PubMed  CAS  Google Scholar 

  26. Cordero OJ, Salgado FJ, Nogueira M. On the origin of serum CD26 and its altered concentration in cancer patients. Cancer Immunol Immunother. 2009;58:1723–47.

    Article  PubMed  CAS  Google Scholar 

  27. Dohi O, Ohtani H, Hatori M, et al. Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours. Histopathology. 2009;55:432–40.

    Article  PubMed  Google Scholar 

  28. Cordero OJ, Imbernon M, Chiara LD, et al. Potential of soluble CD26 as a serum marker for colorectal cancer detection. World J Clin Oncol. 2011;2:245–61.

    Article  PubMed  Google Scholar 

  29. Abe M, Havre PA, Urasaki Y, et al. Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines. BMC Cancer. 2011;11:51.

    Article  PubMed  CAS  Google Scholar 

  30. De Chiara L, Rodríguez-Piñeiro AM, Rodríguez-Berrocal FJ, et al. Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas. BMC Cancer. 2010;10:333.

    Article  PubMed  Google Scholar 

  31. Liu AY, Vêncio RZ, Page LS, Ho ME, Loprieno MA, True LD. Bladder expression of CD cell surface antigens and cell-type-specific transcriptomes. Cell Tissue Res. 2012;348:589–600.

    Article  PubMed  CAS  Google Scholar 

  32. Del Rio P, Crafa P, Papadia C, et al. Is CD10 a reliable marker of invasive colorectal cancer? Ann Ital Chir. 2011;82:279–82.

    PubMed  Google Scholar 

  33. Heidarpour M, Rajabi P, Sajadi F. CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma. J Res Med Sci. 2011;16:938–44.

    PubMed  Google Scholar 

Download references

Conflict of interest

The authors report no conflict of interests.

Author information

Authors and Affiliations

  1. Orthopedics Department, Zhongshan City People’s Hospital, Zhongshan, 528403, China

    Hongtao Zhang

  2. Orthopedics Department, Affiliated Hospital of Putian University, Putian, 351100, China

    Haibin Lin & Guoli Chen

  3. Oncology Department, Nanfang Hospital, The Southern Medical University, Guangzhou, 510515, China

    Xiaoqiong Mo

  4. Orthopedics Department, Zhujiang Hospital, The Southern Medical University, Guangzhou, 510282, China

    Lijun Lin

Authors
  1. Hongtao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haibin Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoqiong Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guoli Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lijun Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lijun Lin.

Additional information

Hongtao Zhang, Haibin Lin and Xiaoqiong Mo have contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, H., Lin, H., Mo, X. et al. Synergistic relationship between dipeptidyl peptidase IV and neutral endopeptidase expression and the combined prognostic significance in osteosarcoma patients. Med Oncol 30, 608 (2013). https://doi.org/10.1007/s12032-013-0608-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0608-6

Keywords

Search

Navigation