title: High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma.
abstract: BACKGROUND
  Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC).
  
  
  METHODS
  A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17).
  
  
  CONCLUSIONS
  CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.
authors.affiliation: St. Vincent's Centre for Applied Medical Research, Sydney, Australia.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Fisher
authors.forename: Angelique J
authors.initials: AJ
authors.lastname: Levert-Mignon
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lord
authors.forename: Natalia K
authors.initials: NK
authors.lastname: Botelho
authors.forename: Araluen K
authors.initials: AK
authors.lastname: Freeman
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Thomas
authors.forename: Dan
authors.initials: D
authors.lastname: Falkenback
authors.forename: Antony
authors.initials: A
authors.lastname: Wettstein
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.forename: Reginald V
authors.initials: RV
authors.lastname: Lord
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D020059:Cathepsin E / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004947:Esophagus / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008679:Metaplasia / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D020059:Cathepsin E; C533925:CTSE protein, human