Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma

Summary

Kallikreins are a subgroup of serine proteases that are involved in the post-translational processing of polypeptide precursors. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. Human kallikrein gene 7 (KLK7; HSCCE) is a new member of the human kallikrein gene family. KLK7 is expressed in normal breast tissue and is up-regulated in breast cancer cells by estrogens and glucocorticoids. In the present study, expression of the KLK7 gene in 92 breast cancer tissues was analyzed by reverse transcription-PCR (RT-PCR) and direct sequencing of several samples. The results were correlated with other clinicopathological variables and patient outcome. KLK7 gene expression was significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and patients with positive progesterone receptors (p = 0.022). Survival analysis showed that breast cancer patients with KLK7 positive tumors have relatively shorter disease-free survival (DFS) and overall survival (OS) than patients with KLK7 negative tumors. These data suggest that KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients.

Keywords

KLK7 - hK7 - HSCCE - breast cancer - kallikrein - KLK - prognosis - tumor markers

• References

• 1 Yousef G, Chang A, Scorilas A. et al. Genomic organization of the human kallikrein locus on chromosome 19q13.3-q13.4. Biochem Bioph Res Co 2000; 276: 125-33.
• 2 Diamandis EP, Yousef GM, Luo LY. et al. The new kallikrein gene family-implications in carcinogenesis. Trends Endocrinol Metab 2000; 11: 54-60.
• 3 Bhoola K, Ramsaroop R, Plendl J. et al. Kallikrein and kinin receptor in inflammation and cancer. Biol Chem 2001; 382: 77-89.
• 4 Bhoola K, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens and kininases. Pharmacol Rev 1992 44: 1-80.
• 5 Bhoola K. Translocation of the neutrophil kinin moiety and changes in the regulation of kinin receptors in inflammation. Immunopharmacology 1996; 33: 247-56.
• 6 Lundstrom A, Egelrud T. Stratum corneum chymotryptic enzyme: a proteinase which may be generally present in the stratum corneum and with a possible involvement in desquamation. Acta Derm Venereol 1991; 71: 471-4.
• 7 Tanimoto H, Underwood LJ, Shigemasa K. et al. The stratum corneum chymotryptic enzyme that mediates shedding and desquamation of skin cells is highly overexpressed in ovarian tumor cells. Cancer 1999; 86: 2074-82.
• 8 Hansson L, Stromqvist M, Backman A. et al. Cloning, expression and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase. J Biol Chem 1994; 269: 19420-6.
• 9 Yousef GM, Scorilas A, Magklara A. et al. The KLK7 (PRSS6) gene, endoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family-genomic characterization, mapping, tissue expression and hormonal regulation. Gene 2000; 254: 119-28.
• 10 Ekholm E, Egelrud T. Stratum corneum chymotriptic enzyme in psoriasis. Arch Dermatol Res 1999; 29: 195-200.
• 11 Kyriakopoulou LG, Yousef GM, Scorilas A. et al. Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer. Clin Biochem 2003; 36: 135-43.
• 12 Scott-Conor CE, Christie DW. Cancer staging using the American Joint Committee on Cancer TNM System. J Am Coll Surg 1995; 181 (02) 182-8.
• 13 Doussal VL, Tubiana-Hulin M, Friedman S. et al. Prognostic value of histilogigic grade nuclear components of Scarff-Bloom-Richardson SBR): an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 1989; 64: 1914-22.
• 14 Dressler LG, Seamer LC, Owens MA. et al. Dna flow cytometry and prognostic factors in 1131 frozen breast cancer specimens. Cancer(Phila) 1988; 61: 420-7.
• 15 Scorilas A, Talieri M, Ardavanis A. et al. Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: A new independent prognostic marker in primary breast cancer. Cancer Res 2000; 60: 5427-33.
• 16 Scatchard G. The attraction of proteins for small molecules and ions. Ann NY Acad Sci 1949; 51: 660-72.
• 17 Alexiera-Figusch J, Van Putten WLS, Blankestein MA. et al. The prognostic value and relationships of patient characteristics, estrogen and progestin receptors and site of relapse in primary breast cancer. Cancer (Phila) 1988; 61: 758-68.
• 18 Reiher A, Kolb R, Reiner G. et al. Prognostic significance of steroid hormone receptor and histopathological characterization of human breast cancer. J Cancer Res Clin Oncol 1987; 113: 285-90.
• 19 Cox DR. Regression models and life tables R. Stat Soc. B 1972; 34: 187-202.
• 20 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.
• 21 Diamandis EP, Yousef GM, Clements J. et al. New nomenclature for the human tissue kallikrein gene family. Clin Chem 2000; 46: 1855-8.
• 22 Sondell B, Thornell LE, Egelrud T. Evidence that stratum corneum chymotryptic enzyme is transported to the stratum corneum extracellular space via lamellar bodies. J Invest Dermatol 1995; 104: 819-23.
• 23 Sondell B, Dysberg P, Anneroth GK. et al. Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa. Acta Drm Venereol 1996; 76: 177-81.
• 24 Sondell B, Thornell LE, Stigbrand T. et al. Immunolocalization of stratum corneum chymotriptic enzyme in human skin and oral epithelium with monoclonal antibodies: evidence of a proteinase specifically expressed in keratiniing squamous epithelia. J Histochem Cytochem 1994; 42: 459-65.
• 25 Tanimoto H, Yan Y, Clarke J. et al. Hepsin: a cell surface serine protease identified in hepatoma cells is overexpressed in ovarian cancer. Cancer Res 1997; 57: 2884-7.
• 26 Egelrud T. Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. J Invest Dermatol 1993; 101: 200-4.
• 27 Shigemasa K, Tanimoto H, Underwood LJ. et al. Expression of the protease inhibitor antileukoprotease and the serine protease stratum corneum chymotryptic enzyme (SCCE) is coordinated in ovarian tumors. Int J Gynecol Cancer 2001; 11: 454-61.
• 28 Franzke CW, Baici A, Bartels J. et al. Antileukoprotease inhibits stratum corneum chymotryptic enzyme. J Biol Chem 1996; 271: 21886-90.
• 29 Yousef GM, Scorilas A, Kyriakolpoulou LG. et al. Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer. Clin Chem 2002; 48: 1241-50.
• 30 Luo Y, Katsaros D, Scorilas A. et al. Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. Clin Cancer Res 2001; 07: 2372-9.
• 31 Luo LY, Bunting P, Scorilas A. et al. Human kallikrein 10: A novel tumor marker for ovarian carcinoma?. Clin Chim Acta 2001; 306: 111-8.
• 32 Chang A, Yousef G, Scorilas A. et al. Human Kallikrein gene 13 (KLK13) expression by quantitative RT-PCR: An independent indicator of favorable prognosis in breast cancer. Br J Cancer 2002; 86: 1457-64.
• 33 Yousef GM, Kyriakopoulou L, Scorilas A. et al. Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker. Cancer Res 2001; 61: 7811-8.
• 34 Yousef GM, Scorilas A, Nakamura T. et al. The prognostic value of the human kallikrein gene 9 (KLK9) in breast cancer. Breast Cancer Res Treat 2003; 78: 149-58.
• 35 Diamandis EP, Scorilas A, Fracchioli S. et al. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol 2003; 21 (06) 1035-43.
• 36 Yousef GM, Fracchioli S, Scorilas A. et al. Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer. Am J Clin Pathol 2003; 119: 346-55.
• 37 Luo LY, Katsaros D, Scorilas A. et al. The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis. Cancer Res 2003; 63: 807-11.
• 38 Yousef GM, Borgono CA, Scorilas A. et al. Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis. Br J Cancer 2002; 87: 1287-93.
• 39 Hoffman BR, Katsaros D, Scorilas A. et al. Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker. Br J Cancer 2002; 87: 763-71.