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FOXO3 expression during colorectal cancer progression: Biomarker potential reflects a tumour suppressor role.

FOXO3 expression during colorectal cancer progression: Biomarker potential reflects a tumour suppressor role.
FOXO3 expression during colorectal cancer progression: Biomarker potential reflects a tumour suppressor role.
Background: In previous studies, the Forkhead/winged-helix-box-class-O3 (FOXO3) transcription factor has displayed both tumour suppressive and metastasis-promoting properties.
To clarify its role in human colorectal cancer (CRC) progression, we examined in vivo FOXO3 expression at key points of the metastatic cascade.

Methods: Formalin-fixed paraffin-embedded resection specimens from normal colon, adenomas, primary CRC specimens of different pathological stage and CRC specimens with matched liver metastases were used to generate three separate custom-designed tissue microarray (TMA) representations of metastatic progression. Triplicate cores, immunostained for FOXO3 were scored semiquantitatively by two investigators.

Results: The FOXO3 expression is significantly reduced in CRC specimens compared with normal tissue, and progressive FOXO3 downregulation is associated with advancing pathological stage. In addition, recurrent stage I/II primary tumours show a significantly lower FOXO3 expression compared with stage-matched non-recurrent tumours. When stratified according to high and low FOXO3 expression, mean disease-free survival in the low-expressing group was 28 months (95% CI 15.8–50.6) compared with 64 months (95% CI 52.9–75.4) in the high-expressing group.

Conclusion: We have demonstrated an association between low FOXO3 expression and CRC progression in vivo using purpose-designed TMAs. Forkhead/winged-helix-box-class-O3 may represent a novel biomarker of nodal and distant disease spread with clinical utility in CRC.

colorectal neoplasms, neoplasm metaastasis, foxo3 protein, tissue microarray analysis
0007-0920
387-394
Bullock, M.D.
1c251c82-7dc6-4df8-9ba2-6b55a4daf947
Bruce, A.
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Sreekumar, R.
057a5adf-52f1-4893-bfc3-f858d83f676f
Curtis, N
1b87d286-995f-4fea-a008-aa5dd7f634b7
Cheung, T.
a54dae69-47bc-40a1-8de8-81257ad4b631
Reading, Isabel
6f832276-87b7-4a76-a9ed-b4b3df0a3f66
Primrose, J.N.
d85f3b28-24c6-475f-955b-ec457a3f9185
Ottensmeier, C.
42b8a398-baac-4843-a3d6-056225675797
Packham, G.K.
fdabe56f-2c58-469c-aadf-38878f233394
Thomas, G.
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Mirnezami, A.H.
b3c7aee7-46a4-404c-bfe3-f72388e0bc94
Bullock, M.D.
1c251c82-7dc6-4df8-9ba2-6b55a4daf947
Bruce, A.
0e0148fa-8760-4724-b10a-8ea55883328a
Sreekumar, R.
057a5adf-52f1-4893-bfc3-f858d83f676f
Curtis, N
1b87d286-995f-4fea-a008-aa5dd7f634b7
Cheung, T.
a54dae69-47bc-40a1-8de8-81257ad4b631
Reading, Isabel
6f832276-87b7-4a76-a9ed-b4b3df0a3f66
Primrose, J.N.
d85f3b28-24c6-475f-955b-ec457a3f9185
Ottensmeier, C.
42b8a398-baac-4843-a3d6-056225675797
Packham, G.K.
fdabe56f-2c58-469c-aadf-38878f233394
Thomas, G.
11e04ba6-cee3-4ac9-ab43-4184887ebf9b
Mirnezami, A.H.
b3c7aee7-46a4-404c-bfe3-f72388e0bc94

Bullock, M.D., Bruce, A., Sreekumar, R., Curtis, N, Cheung, T., Reading, Isabel, Primrose, J.N., Ottensmeier, C., Packham, G.K., Thomas, G. and Mirnezami, A.H. (2013) FOXO3 expression during colorectal cancer progression: Biomarker potential reflects a tumour suppressor role. British Journal of Cancer, 109 (2), 387-394. (doi:10.1038/bjc.2013.355). (PMID:23828518)

Record type: Article

Abstract

Background: In previous studies, the Forkhead/winged-helix-box-class-O3 (FOXO3) transcription factor has displayed both tumour suppressive and metastasis-promoting properties.
To clarify its role in human colorectal cancer (CRC) progression, we examined in vivo FOXO3 expression at key points of the metastatic cascade.

Methods: Formalin-fixed paraffin-embedded resection specimens from normal colon, adenomas, primary CRC specimens of different pathological stage and CRC specimens with matched liver metastases were used to generate three separate custom-designed tissue microarray (TMA) representations of metastatic progression. Triplicate cores, immunostained for FOXO3 were scored semiquantitatively by two investigators.

Results: The FOXO3 expression is significantly reduced in CRC specimens compared with normal tissue, and progressive FOXO3 downregulation is associated with advancing pathological stage. In addition, recurrent stage I/II primary tumours show a significantly lower FOXO3 expression compared with stage-matched non-recurrent tumours. When stratified according to high and low FOXO3 expression, mean disease-free survival in the low-expressing group was 28 months (95% CI 15.8–50.6) compared with 64 months (95% CI 52.9–75.4) in the high-expressing group.

Conclusion: We have demonstrated an association between low FOXO3 expression and CRC progression in vivo using purpose-designed TMAs. Forkhead/winged-helix-box-class-O3 may represent a novel biomarker of nodal and distant disease spread with clinical utility in CRC.

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More information

Published date: 4 July 2013
Keywords: colorectal neoplasms, neoplasm metaastasis, foxo3 protein, tissue microarray analysis
Organisations: Cancer Sciences, Primary Care & Population Sciences

Identifiers

Local EPrints ID: 359508
URI: https://eprints.soton.ac.uk/id/eprint/359508
ISSN: 0007-0920
PURE UUID: 3aeefe2d-2fbc-41cc-8fa0-ee1d04a2d197
ORCID for Isabel Reading: ORCID iD orcid.org/0000-0002-1457-6532
ORCID for J.N. Primrose: ORCID iD orcid.org/0000-0002-2069-7605
ORCID for G.K. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 04 Nov 2013 11:03
Last modified: 20 Jul 2019 01:19

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Contributors

Author: M.D. Bullock
Author: A. Bruce
Author: R. Sreekumar
Author: N Curtis
Author: T. Cheung
Author: Isabel Reading ORCID iD
Author: J.N. Primrose ORCID iD
Author: C. Ottensmeier
Author: G.K. Packham ORCID iD
Author: G. Thomas
Author: A.H. Mirnezami

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