Network mapping of molecular biomarkers influencing radiation response in rectal cancer

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Title: Network mapping of molecular biomarkers influencing radiation response in rectal cancer
Authors: Poynter, L
Mirnezami, R
Galea, D
Veselkov, K
Nicholson, J
Takats, Z
Darzi, A
Kinross, J
Mirnezami, A
Item Type: Journal Article
Abstract: Introduction Pre-operative radiotherapy (RT) has an important role in the management of locally advanced rectal cancer (RC). Tumour regression following RT shows marked variability and robust molecular methods are needed with which to predict likely response. The aim of this study was to review the current published literature and employ Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC. Methods A systematic review of electronic bibliographic databases (MEDLINE, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and non-significant results were included in the analysis. Significance was binarized based on uni- and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in rectal cancer radiation response. Results 72 individual biomarkers, across 74 studies, were identified through review. On highest order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity. Conclusions Homogenising biomarker data from original articles using controlled GO terminology demonstrates that cellular mechanisms of response to radiotherapy in RC - in particular the metabolic response to radiotherapy - may hold promise in developing radiotherapeutic biomarkers with which to predict, and in the future modulate, radiation response.
Issue Date: 10-Feb-2019
Date of Acceptance: 23-Jan-2019
URI: http://hdl.handle.net/10044/1/67243
DOI: https://dx.doi.org/10.1016/j.clcc.2019.01.004
ISSN: 1533-0028
Publisher: Elsevier
Journal / Book Title: Clinical Colorectal Cancer
Copyright Statement: © 2019 The Authors. Published by Elsevier Inc. Accepted manuscript available open access under a CC-BY-NC-ND Attribution 4.0 Licence 9https://creativecommons.org/licenses/by-nc-nd/4.0/)
Sponsor/Funder: Bowel Disease Research Foundation
Keywords: Oncology & Carcinogenesis
Publication Status: Published online
Online Publication Date: 2019-02-10
Appears in Collections:Division of Surgery
Faculty of Medicine



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