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Selected Works of Sally Lord
Article
High expression of Cathepsin E in tissues but not blood of patients with Barrett’s esophagus and adenocarcinoma
Annals of Surgical Oncology (2014)
  • Oliver Fisher, St Vincent's Centre for Applied Medical Research
  • Angelique Levert-Mignon, St Vincent's Centre for Applied Medical Research
  • Sally Lord, The University of Notre Dame Australia
  • Natalia Botelho, St Vincent's Centre for Applied Medical Research
  • Araluen Freeman, St Vincent's Centre for Applied Medical Research
  • Melissa Thomas, St Vincent's Centre for Applied Medical Research
  • Dan Falkenback, Lund University
  • Anthony Wettstein, St. Vincents Clinic
  • David Whiteman, Queensland Institute of Medical Research
  • Yuri Bobryshev, St. Vincents Centre for Applied Medical Research
  • Reginald Lord, The University of Notre Dame Australia
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Abstract
Background.
Cathepsin E (CTSE), an aspartic proteinase,
is  differentially  expressed  in  the  metaplasia–dysplasia–
neoplasia sequence of gastric and colon cancer. We eval-
uated   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
C
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.
Disciplines
Publication Date
2014
DOI
10.1245/s10434-014-4155-y
Citation Information
Fisher, O., Levert-Mignon, A., Lord, S., Botelho, N., Freeman, A., Thomas, M., Falkenback, D., Wettstein, A., Whiteman, D., Bobryshev, Y., and Lord, R. (2014). High expression of Cathepsin E in tissues but not bloodof patients with Barretts esophagus and adenocarcinoma. Annals of Surgical Oncology, 22(7), 2431-2438. DOI: 10.1245/s10434-014-4155-y