The relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients

Quinn, J. A. , Bennett, L., Patel, M., Frixou, M., Park, J. H., Roseweir, A., Horgan, P. G., McMillan, D. C. and Edwards, J. (2020) The relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients. Histology and Histopathology: Cellular and Molecular Biology, 35(6), pp. 569-578. (doi: 10.14670/HH-18-168) (PMID:31592535)

Abstract

The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway colorectal in cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined. All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer-specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil-lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033). Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort.

• Item Type: Articles
• Additional Information: Mikaela Frixou was supported by a Medical Research Scotland – Vacation Scholarship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Quinn, Dr Jean
• Authors: Quinn, J. A., Bennett, L., Patel, M., Frixou, M., Park, J. H., Roseweir, A., Horgan, P. G., McMillan, D. C., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Histology and Histopathology: Cellular and Molecular Biology
• Publisher: Universidad de Murcia
• ISSN: 0213-3911
• ISSN (Online): 1699-5848
• Published Online: 08 October 2019
• Copyright Holders: Copyright © 2019 Universidad de Murcia
• First Published: First published in Histology and Histopathology: Cellular and Molecular Biology 35(6): 569-578
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher