title: Downregulated KLK13 expression in bladder cancer highlights tumor aggressiveness and unfavorable patients' prognosis.
abstract: OBJECTIVE
  Despite recent research advantages on the molecular and subcellular background, bladder cancer (BlCa) remains a clinically neglected malignancy. This is strongly reflected by the generic approach of disease diagnosis and management. Additionally, patients' prognosis became a rather demanding task due to the great disease heterogeneity. Here, we aimed to evaluate, for the first time, the clinical value of KLK13 in BlCa.
  
  
  METHODS
  A total of 279 bladder specimens (137 tumors, 107 adjacent normal tissues and 35 healthy samples) were included. Total RNA was extracted, reverse transcribed, and KLK13 expression was assessed by quantitative real-time PCR.
  
  
  RESULTS
  KLK13 expression is significantly increased in bladder tumors compared to normal adjacent epithelium. However, reduced KLK13 expression is correlated with disease aggressiveness, including higher tumor stage and grade, and high-risk TaT1 tumors according to the EORTC stratification. Moreover, Kaplan-Meier and Cox regression analysis highlighted the prognostic value of the reduced KLK13 expression for the prediction of TaT1 patients' recurrence and shorter disease-free survival following TURBT. Finally, the combination of KLK13 expression with EORTC-risk stratification results to an improved prediction of TaT1 patients' outcome.
  
  
  CONCLUSIONS
  This first clinical study of KLK13 in BlCa reveals its deregulated expression in bladder tumors and highlights KLK13 as a promising marker for improving TaT1 patients' prognosis following treatment.
authors.affiliation: First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527, Athens, Greece. ttokas@yahoo.com.|Department of Urology and Andrology, General Hospital Hall in Tirol, Milser Str. 10, 6060, Hall in Tirol, Austria. ttokas@yahoo.com.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tokas
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701, Athens, Greece.
authors.forename: Margaritis
authors.initials: M
authors.lastname: Avgeris
authors.affiliation: First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Alamanis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527, Athens, Greece.
authors.forename: Konstantinos G
authors.initials: KG
authors.lastname: Stravodimos
authors.affiliation: First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527, Athens, Greece.
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Constantinides
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C470778:KLK13 protein, human; D007610:Kallikreins
keywords: Bladder tumors; KLK; KLKs; Kallikrein 13; Kallikrein-related peptidase 13; Kallikrein-related peptidases