Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma
Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma
Background: esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.
Aims: to examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma.
Methods: expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5?-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues.
Results: there was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues.
Conclusion: nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma
adenocarcinoma of the esophagus, androgen receptors, FK506-binding protein 5, steroids, prognosis
433
Smith, Eric
d2445970-3034-4a7f-9465-87f79f636ea6
Palethorpe, Helen M.
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Ruszkiewicz, Andrew R.
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Edwards, Suzanne
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Leach, Damien A.
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Underwood, Tim J.
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Need, Eleanor F.
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Drew, Paul A.
3312262e-cf84-45d3-a555-f80f315bd361
1 February 2016
Smith, Eric
d2445970-3034-4a7f-9465-87f79f636ea6
Palethorpe, Helen M.
caa72471-7689-4a2c-ae3c-edd42ac9f1da
Ruszkiewicz, Andrew R.
fb6df2b2-5371-4da0-abe9-8cab88a4f406
Edwards, Suzanne
bff7bd5d-e1c1-4844-b653-c289d90e2df3
Leach, Damien A.
2344b7c4-56f6-4cc5-8c5d-48a23b0e44c6
Underwood, Tim J.
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Need, Eleanor F.
0beeb84c-a0a2-48e1-a949-a988ce11ff38
Drew, Paul A.
3312262e-cf84-45d3-a555-f80f315bd361
Smith, Eric, Palethorpe, Helen M., Ruszkiewicz, Andrew R., Edwards, Suzanne, Leach, Damien A., Underwood, Tim J., Need, Eleanor F. and Drew, Paul A.
(2016)
Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma.
Digestive Diseases and Sciences, 61 (2), .
(doi:10.1007/s10620-015-3909-0).
(PMID:26467701)
Abstract
Background: esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.
Aims: to examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma.
Methods: expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5?-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues.
Results: there was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues.
Conclusion: nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma
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e-pub ahead of print date: 14 October 2015
Published date: 1 February 2016
Keywords:
adenocarcinoma of the esophagus, androgen receptors, FK506-binding protein 5, steroids, prognosis
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 383049
URI: http://eprints.soton.ac.uk/id/eprint/383049
ISSN: 0163-2116
PURE UUID: b1346ebd-9e9d-40fd-8b82-1e844e7717cc
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Date deposited: 05 Nov 2015 12:28
Last modified: 15 Mar 2024 03:17
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Contributors
Author:
Eric Smith
Author:
Helen M. Palethorpe
Author:
Andrew R. Ruszkiewicz
Author:
Suzanne Edwards
Author:
Damien A. Leach
Author:
Eleanor F. Need
Author:
Paul A. Drew
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