title: Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma.
abstract: KLK6 is a secreted trypsin-like serine protease. KLK6 mRNA expression and its association with colon cancer (CC) progression was studied using quantitative real-time PCR. We examined the expression of KLK6 in 232 colon tissues (cancerous, non-cancerous, and adenomatous). We proved that KLK6 expression in CC behaves as a continuous variable, as its expression correlates significantly with increasing tumor stage (p=0.004) and histological grade (p=0.007). Interestingly, the expression of KLK6 in adenomas was significantly higher than that in the cancerous or non-cancerous tissues examined (p<0.001). Cox proportional hazard regression model using univariate analysis revealed that positive KLK6 expression is a significant factor for disease-free survival (DFS) (p=0.017) and overall survival (OS) (p=0.002) of patients. Kaplan-Meier survival curves demonstrated that KLK6-negative expression is significantly associated with longer DFS (p=0.009) and OS (p=0.001). ROC analysis showed that KLK6 expression has significant discriminatory power in distinguishing cancerous from non-cancerous colon tissues (p<0.001), or cancerous from adenoma tissues (p=0.001), or adenoma from non-cancerous colon tissues (p<0.001). Additionally, strong KLK6 immunostaining was seen in the cancer cells of selected CC sections, as well as in glandular cells and inflammatory cells of adenomas. In conclusion, KLK6 may represent a potential unfavorable prognostic biomarker for CC.
authors.forename: Athina
authors.initials: A
authors.lastname: Vakrakou
authors.forename: Marina
authors.initials: M
authors.lastname: Devetzi
authors.forename: Georgia
authors.initials: G
authors.lastname: Papachristopoulou
authors.forename: Apostolos
authors.initials: A
authors.lastname: Malachias
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Dimitris
authors.initials: D
authors.lastname: Xynopoulos
authors.forename: Maroulio
authors.initials: M
authors.lastname: Talieri
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D012372:ROC Curve
chemical_list: C103551:KLK6 protein, human; D007610:Kallikreins