title: Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.
abstract: 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 (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<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.
authors.forename: David L
authors.initials: DL
authors.lastname: Kolin
authors.forename: Keiyan
authors.initials: K
authors.lastname: Sy
authors.forename: Fabio
authors.initials: F
authors.lastname: Rotondo
authors.forename: Mena N
authors.initials: MN
authors.lastname: Bassily
authors.forename: Kalman
authors.initials: K
authors.lastname: Kovacs
authors.forename: Christine
authors.initials: C
authors.lastname: Brezden-Masley
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Streutker
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D020840:Tissue Kallikreins / Q000378:metabolism*; D055815:Young Adult
chemical_list: C100936:KLK10 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins; D020840:Tissue Kallikreins