title: Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Improvements in the understanding of its molecular mechanism and the characterisation of CRC-specific biomarkers facilitating early detection are considered to increase overall survival.
  
  
  METHODS
  A meta-analysis of microarray and Serial Analysis of Gene Expression (SAGE) has been performed to identify differentially regulated genes in CRC. Dipeptidase 1 (DPEP1/MDP/RDP) and Syntenin-2 (SDCBP2/SITAC18) were found to be differentially expressed in tumour tissue compared with normal mucosa. Expression of DPEP1 was assessed in a validation set of 87 normal mucosa samples, 20 hyperplastic polyps, 46 CR adenomas with low- and high-grade intraepithelial neoplasia (IEN) and 217 well-documented CRCs by immunohistochemistry and partially by immunoblotting and real-time PCR.
  
  
  RESULTS
  Expression of DPEP1 was specifically increased in human CRC tissue samples compared with normal mucosa (P<0.0001, Mann-Whitney U-test), showing a striking upregulation in high-grade compared with low-grade IEN. Furthermore, high DPEP1 expression was found to strongly correlate with histological stage (P<0.0001, chi-square test) as well as localisation (P<0.0001, chi-square test) and has been recognised as an independent adverse prognostic factor, showing significant prognostic values with an ROC (receiver operating characteristic)-AUC of 0.9230.
  
  
  CONCLUSIONS
  Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany. eisenach@biochem.mpg.de
authors.forename: P A
authors.initials: PA
authors.lastname: Eisenach
authors.forename: E
authors.initials: E
authors.lastname: Soeth
authors.forename: C
authors.initials: C
authors.lastname: Röder
authors.forename: G
authors.initials: G
authors.lastname: Klöppel
authors.forename: J
authors.initials: J
authors.lastname: Tepel
authors.forename: H
authors.initials: H
authors.lastname: Kalthoff
authors.forename: B
authors.initials: B
authors.lastname: Sipos
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D004150:Dipeptidases / Q000096:biosynthesis* / Q000235:genetics; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D004150:Dipeptidases; C549872:dipeptidase 1