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High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma

Fisher, Oliver M.; Levert-Mignon, Angelique J.; Lord, Sarah J.; Botelho, Natalia K.; Freeman, Araluen K.; Thomas, Melissa L.; Falkenback, Dan LU ; Wettstein, Antony; Whiteman, David C. and Bobryshev, Yuri V., et al. (2015) In Annals of Surgical Oncology 22(7). p.2431-2438
Abstract
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). 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... (More)
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). 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. Median CTSE mRNA expression levels were a parts per thousand yen1,000-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). 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. (Less)
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Annals of Surgical Oncology
volume
22
issue
7
pages
2431 - 2438
publisher
Springer
external identifiers
  • wos:000355748300046
  • scopus:84930472858
ISSN
1534-4681
DOI
10.1245/s10434-014-4155-y
language
English
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yes
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93de10ab-ed28-47e3-8ece-1a085ff92348 (old id 7602061)
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2015-08-03 10:11:19
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2017-07-02 04:14:08
@article{93de10ab-ed28-47e3-8ece-1a085ff92348,
  abstract     = {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). 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. Median CTSE mRNA expression levels were a parts per thousand yen1,000-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). 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.},
  author       = {Fisher, Oliver M. and Levert-Mignon, Angelique J. and Lord, Sarah J. and Botelho, Natalia K. and Freeman, Araluen K. and Thomas, Melissa L. and Falkenback, Dan and Wettstein, Antony and Whiteman, David C. and Bobryshev, Yuri V. and Lord, Reginald V.},
  issn         = {1534-4681},
  language     = {eng},
  number       = {7},
  pages        = {2431--2438},
  publisher    = {Springer},
  series       = {Annals of Surgical Oncology},
  title        = {High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma},
  url          = {http://dx.doi.org/10.1245/s10434-014-4155-y},
  volume       = {22},
  year         = {2015},
}