Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer

• Published in: Biological chemistry Vol. 395; no. 9; pp. 1087 - 1093
• Main Authors: Kolin, David L., Sy, Keiyan, Rotondo, Fabio, Bassily, Mena N., Kovacs, Kalman, Brezden-Masley, Christine, Streutker, Catherine J., Yousef, George M.
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.09.2014
• Subjects: Adult; Aged; Aged, 80 and over; Female; gastric cancer; Humans; Immunohistochemistry; kallikreins; Kallikreins - metabolism; Kaplan-Meier Estimate; KLK10; KLK6; Male; Middle Aged; personalized medicine; Prognosis; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tissue Kallikreins - metabolism; tissue microarray analysis; tumor markers; Young Adult
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/hsz-2014-0143

The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement ( =0.002) and was predictive of advanced-stage disease ( <0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival ( =0.04). KLK10 overexpression was also a predictor of advanced-stage disease ( <0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer.