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Expression analysis and clinical evaluation of kallikrein-related peptidase 10 (KLK10) in colorectal cancer

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Tumor Biology

Abstract

Kallikrein-related peptidases (KLKs) represent a serine protease family having 15 members. KLK10 is a secreted protease with a trypsin-like activity. The function of KLK10 is poorly understood, although it has been suggested that KLK10 may function as a tumor suppressor gene. In human cancer, KLK10 gene shows organ-specific up- or down-regulation. Since KLKs are promising tumor biomarkers, the examination of KLK10 mRNA expression and its association with colorectal cancer (CRC) progression was studied using semi-quantitative PCR. One hundred and nineteen primary CRC specimens were examined for which follow-up information was available for a median period of 29 months (range, 1–104 months). KLK10 expression was found to be significantly associated with TNM stage (p = 0.028). Cox proportional hazard regression model using univariate analysis revealed for the first time that high status KLK10 expression is a significant factor for disease-free survival (DFS; p = 0.002) and overall survival (OS; p = 0.026) of patients. Kaplan–Meier survival curves demonstrated that KLK10 expression of low status is significantly associated with longer DFS (p = 0.001) as well as OS (p = 0.021), suggesting that KLK10 gene expression may be used as a marker of unfavorable prognosis for CRC. As the epigenetics of cancer are unraveled, KLK10 may represent not only a novel biomarker, but also a promising future therapeutic target for the disease.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  2. Borgono CA, Diamandis EP. The emerging roles of human kallikreins in cancer. Nat Rev Cancer. 2004;4:876–90.

    Article  PubMed  CAS  Google Scholar 

  3. Lawrence MG, Lai J, Clements JA. Kallikreins on steroids: structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus. Endocr Rev. 2010;31:407–46.

    Article  PubMed  CAS  Google Scholar 

  4. Sotiropoulou G, Pampalakis G, Diamandis EP. Funcional roles of human kallikrein-related peptidases. J Biol Chem. 2009;284:32989–94.

    Article  PubMed  CAS  Google Scholar 

  5. Sotiropoulou G, Pampalakis G. Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation. Biol Chem. 2010;391:321–31.

    Article  PubMed  CAS  Google Scholar 

  6. Paliouras M, Borgono C, Diamandis E. Human tissue kallikreins: the cancer biomarker family. Cancer Lett. 2007;249:61–79.

    Article  PubMed  CAS  Google Scholar 

  7. Christophi GP, Isackson PJ, Blaber S, Blaber M, Rodriquez M, Scarisbrick IA. Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. J Neurochem. 2004;91:1439–49.

    Article  PubMed  CAS  Google Scholar 

  8. Pampalakis G, Diamandis E, Sotiropoulou G. The epigenetic basis for the aberrant expression of kallikreins in human cancers. Biol Chem. 2006;387:795–9.

    Article  PubMed  CAS  Google Scholar 

  9. Emami N, Diamandis EP. Human tissue kallikreins: a road under construction. Clin Chim Acta. 2007;381:78–84.

    Article  PubMed  CAS  Google Scholar 

  10. Hekim C, Riipi T, Weisell J, Narvanen A, Koistinen R, Stenman U-H, et al. Identification of IGFBP-3 fragments generated by KLK2 and prevention of fragmentation by KLK2-inhibiting peptides. Biol Chem. 2010;391:475–9.

    Article  PubMed  CAS  Google Scholar 

  11. Avgeris M, Mavridis K, Scorilas A. Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies. Biol Chem. 2010;391(5):505–11.

    Article  PubMed  CAS  Google Scholar 

  12. Talieri M, Li L, Zheng Y, Alexopoulou DK, Soosaipillai A, Scorilas A, et al. A multiparametric tissue kallikrein-related peptidase panel for colorectal cancer. Br J Cancer. 2009;100:1659–65.

    Article  PubMed  CAS  Google Scholar 

  13. Prezas P, Scorilas A, Yfanti Ch, Viktorov P, Agnanti N, Diamandis EP, et al. Human tissue kallikreins 7 and 8 gene expression in intracranial tumors: a clinical study in Greece. Biol Chem. 2006;387:613–8.

    Google Scholar 

  14. Luo L, Herbrick JA, Scherer SW, Beatty B, Squire J, Diamandis EP. Structural characterization and mapping of the normal epithelial cell-specific 1 gene. Biochem Biophys Res Commun. 1998;247:580–6.

    Article  PubMed  CAS  Google Scholar 

  15. Luo LY, Grass L, Howarth DJC, Thibault P, Ong H, Diamandis EP. Immunofluorometric assay of human kallikrein 10 and its identification in biological fluids and tissues. Clin Chem. 2001;47:237–46.

    PubMed  CAS  Google Scholar 

  16. Yousef GM, White NM, Michael IP, Cho JC, Robb JD, Kurlender L, et al. Identification of new splice variants and differential expression of the human kallikrein 10 gene, a candidate cancer biomarker. Tumour Biol. 2005;26:227–35.

    Article  PubMed  CAS  Google Scholar 

  17. Goyal J, Smith KM, Cowan JM, Wazer DE, Lee SW, Band V. The Role for NES1 serine protease as a novel tumor suppressor. Cancer Res. 1998;58:4782–6.

    PubMed  CAS  Google Scholar 

  18. Luo LY, Grass L, Diamandis EP. Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter. Clin Chim Acta. 2003;337:115–26.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang Y, Song H, Miao Y, Wang R, Chen L. Frequent transcriptional inactivation of kallikrein 10 gene by CpG island hypermethylation in non-small cell lung cancer. Cancer Sci. 2010;101:934–40.

    Article  PubMed  CAS  Google Scholar 

  20. Kioulafa M, Kaklamanis L, Stathopoulos E, Mavroudis D, Georgoulias V. Lianidou ES (2009) kallikrein 10 (KLK10) methylation as a novel prognostic biomarker in early breast cancer. Ann Oncol. 2009;20:1020–5.

    Article  PubMed  CAS  Google Scholar 

  21. Tong WG, Wierda WG, LinE KS-Q, Bekele N, Estov Z, Wei Y, et al. Genome-wide DNA methylation profiling of chronic lymphocytic leukemia allows identification of epigenetically repressed molecular pathways with clinical impact. Epigenetics. 2010;5:499–508.

    Article  PubMed  CAS  Google Scholar 

  22. Feng B, Xu WB, Zheng MH, Ma JJ, Cai Q, Zhang Y, et al. Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer. J Gastroenterol Hepatol. 2006;21:1596–603.

    Article  PubMed  CAS  Google Scholar 

  23. Talieri M, Mathioudaki K, Prezas P, Alexopoulou DK, Diamandis EP, Xynopoulos D, et al. Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer. Thromb Haemost. 2009;101(4):741–7.

    PubMed  CAS  Google Scholar 

  24. Benson III AB, Desch CE, Flynn PJ, et al. Update of American Society of Clinical Oncology colorectal cancer surveillance guidelines. J Clin Oncol. 2000;18:3586–8.

    PubMed  Google Scholar 

  25. Shaw J, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem. 2007;53:1423–32.

    Article  PubMed  CAS  Google Scholar 

  26. Liu X-L, Wazer DE, Watanabe K, Band V. Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression. Cancer Res. 1996;56:3371–9.

    PubMed  CAS  Google Scholar 

  27. Petraki CD, Karavana VN, Luo L-Y, Diamandis EP. Human kallikrein 10 expression in normal tissues by immunohistochemistry. J Histochem Cytochem. 2002;50:1247–61.

    Article  PubMed  CAS  Google Scholar 

  28. Dong Y, Matigian N, Harvey TJ, Samaratunga H, Hooper JD, Clements JA. Tissue-specific promoter utilisation of the kallikrein-related peptidase genes, KLK5 and KLK7, and cellular localisation of the encoded proteins suggest roles in exocrine pancreatic function. Biol Chem. 2008;389:99–109.

    Article  PubMed  CAS  Google Scholar 

  29. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128:683–92.

    Article  PubMed  CAS  Google Scholar 

  30. Li B, Goyal J, Dhar S, Dimri G, Evron E, Sukumar S, et al. CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression. Cancer Res. 2001;61:8014–21.

    PubMed  CAS  Google Scholar 

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Correspondence to Maroulio Talieri.

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Talieri, M., Alexopoulou, D.K., Scorilas, A. et al. Expression analysis and clinical evaluation of kallikrein-related peptidase 10 (KLK10) in colorectal cancer. Tumor Biol. 32, 737–744 (2011). https://doi.org/10.1007/s13277-011-0175-4

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  • DOI: https://doi.org/10.1007/s13277-011-0175-4

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