title: Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact.
abstract: Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases, hormonally regulated, and localized on chromosome 19q13.4. Alternative splicing is a process that plays significant role in the development, physiology, and different diseases, like cancer. Kallikrein family numbers more than 82 alternative transcripts. Understanding the role that those gene transcripts play in various cancer types, could lead to the discovery of diagnostic markers or drug targets. The present study was designed to analyze the expression profile of the splice variants of kallikrein-related peptidase 12 (KLK12) in breast cancer patients and to evaluate their clinical significance. KLK12 splice variants (KLK12sv3 and KLK12sv1/KLK12sv2) were examined in 69 tissue samples of breast cancer using quantitative real-time PCR as well as semi-quantitative PCR. Relative quantitative expression of KLK12 was statistically associated to clinicopathological parameters. From the splice variants examined, statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant. KLK12sv3 is more frequently expressed in tumors of lower grade (p = 0.040), early patient TNM stage (p = 0.024), and smaller tumor size (p = 0.023). Positive KLK12sv3 expression is associated with longer patient disease-free survival (DFS) (p = 0.042) and higher progesterone receptor concentration (p = 0.008). KLK12sv1/KLK12sv2 expression is statistically associated with KLK12sv3 expression (p = 0.001). KLK12sv3 can be regarded as a marker of good prognosis in breast cancer.
authors.affiliation: Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, Saint Savvas Cancer Hospital, 171 Alexandras Avenue, Athens 11522, Greece. talieri@agsavvas-hosp.gr
authors.forename: Maroulio
authors.initials: M
authors.lastname: Talieri
authors.forename: Marina
authors.initials: M
authors.lastname: Devetzi
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Eleana
authors.initials: E
authors.lastname: Pappa
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tsapralis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Missitzis
authors.forename: Alexandros
authors.initials: A
authors.lastname: Ardavanis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007610:Kallikreins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; C497170:KLK12 protein, human; D007610:Kallikreins