Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer

Roseweir, A. K. , Powell, A. G.M.T., Bennett, L., Van Wyk, H. C. , Park, J. , McMillan, D. C. , Horgan, P. G. and Edwards, J. (2016) Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer. Oncotarget, 7(43), pp. 70601-70612. (doi: 10.18632/oncotarget.12134) (PMID:27661110)

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Abstract

In patients with colorectal cancer (CRC), local and systemic inflammatory responses have been extensively reported to associate with cancer survival. However, the specific signalling pathways responsible for inflammatory responses are not clear. The PTEN/Akt pathway is a plausible candidate as it may play a role in mediating inflammation via COX-2, and has been associated with cancer progression. This study therefore examined the relationship between tumour PTEN/Akt/COX-2 expression, inflammatory responses and survival in CRC patients using a tissue microarray. In 201 CRC patients, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (12.0yrs v 7.3yrs, P=0.032), poorer differentiation (P=0.032), venous invasion (P=0.008) and peritoneal involvement (P=0.004). Patients were stratified for peri-nuclear expression of COX-2 to examine associations with inflammatory responses. In patients with absent peri-nuclear COX-2 expression, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (11.9yrs v 5.4yrs, P=0.001), poorer differentiation (P=0.018), venous invasion (P=0.003) and peritoneal involvement (P=0.001). However, no associations were seen with either the local or systemic inflammatory responses. In CRC patients, tumour-specific PTEN/Akt pathway activation was significantly associated with poorer CSS, particularly when peri-nuclear COX-2 expression was absent. However, activation of the PTEN/Akt pathway appears not to be responsible for the regulation of inflammatory responses.

Item Type:Articles
Additional Information:This work was supported by the University of Glasgow.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Park, Mr James and Horgan, Professor Paul and Bennett, Miss Lindsay and McMillan, Professor Donald and Roseweir, Dr Antonia and Edwards, Professor Joanne and Powell, Dr Arfon and Van Wyk, Dr Hester
Authors: Roseweir, A. K., Powell, A. G.M.T., Bennett, L., Van Wyk, H. C., Park, J., McMillan, D. C., Horgan, P. G., and Edwards, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Published Online:20 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Oncotarget 7(43):70601-70612
Publisher Policy:Reproduced under a Creative Commons License

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