title: Parallel overexpression and clinical significance of kallikrein-related peptidases 7 and 14 (KLK7KLK14) in colon cancer.
abstract: Currently available colon cancer (CC) markers lack sensitivity and specificity. Kallikrein-related peptidases (KLKs) present a new class of biomarkers under investigation for diverse diseases, including cancer. KLKs are co-expressed in various tissues participating in proteolytic cascades. KLK7 in human tumours facilitates metastasis by degrading components of the extracellular matrix. KLK14 promotes tumourigenesis by activating proteinase-activated receptors. In the present study we examined the concomitant expression of KLK7 and KLK14 in245 colonic tissue specimens from 175 patients; 70 were pairs of cancerous-normal tissues, 31 were cancerous tissues and 74 were colonic adenomas. We used quantitative real-time PCR and proved that both genes are up-regulated in CC at the mRNA level. Receiver-operating characteristic (ROC) analysis of our results showed that both genes have discriminatory value between CC and adenoma tissues, with KLK14 obtaining greater distinguishing power (area under the curve [AUC]=0.708 for KLK14; AUC=0.669 for KLK7). Current work showed that the two genes are fairly co-expressed in all three types of colon tissues examined (normal rs=0.667, p<0.001, adenomas rs=0.373, p=0.001, carcinomas rs=0.478, p<0.001). KLK14 is associated with shorter disease-free survival (DFS) and overall survival (OS) of patients (p=0.003, p=0.016 respectively), whereas KLK7only with shorter DFS (p=0.004). KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for CC patients with discriminating power between CC and adenoma patients.
authors.affiliation: Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, Saint Savvas Cancer Hospital, 171, Alexandras Avenue, Athens 11522, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Devetzi
authors.forename: Theoni
authors.initials: T
authors.lastname: Trangas
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 / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C425336:KLK14 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins