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Network mapping of molecular biomarkers influencing radiation response in rectal cancer

Network mapping of molecular biomarkers influencing radiation response in rectal cancer
Network mapping of molecular biomarkers influencing radiation response in rectal cancer

Preoperative radiotherapy (RT) plays an important role in the management of locally advanced rectal cancer (RC). Tumor regression after RT shows marked variability, and robust molecular methods are needed to help predict likely response. The aim of this study was to review the current published literature and use Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC. 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 nonsignificant results were included in the analysis. Significance was binarized on the basis of univariate 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 RC radiation response. Seventy-two individual biomarkers across 74 studies were identified. 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. Homogenizing biomarker data from original articles using controlled GO terminology demonstrated that cellular mechanisms of response to RT in RC—in particular the metabolic response to RT—may hold promise in developing radiotherapeutic biomarkers to help predict, and in the future modulate, radiation response.

Neoadjuvant therapy, Radiation tolerance, Radiotherapy, Rectal neoplasms
1533-0028
Poynter, Liam
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Galea, Dieter
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Veselkov, Kirill
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Mirnezami, Alexander
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Kinross, James
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Nicholson, Jeremy
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Takáts, Zoltán
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Darzi, Ara
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Mirnezami, Reza
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Poynter, Liam
832c79ec-8601-4768-851a-84f27c5dd050
Galea, Dieter
552595c2-b248-4bfe-9ede-4a063af1ccef
Veselkov, Kirill
80ba703a-db99-4181-a813-75aecc478294
Mirnezami, Alexander
b3c7aee7-46a4-404c-bfe3-f72388e0bc94
Kinross, James
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Nicholson, Jeremy
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Takáts, Zoltán
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Darzi, Ara
9d83b585-1f16-488c-9fd3-fa750c06247b
Mirnezami, Reza
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Poynter, Liam, Galea, Dieter, Veselkov, Kirill, Mirnezami, Alexander, Kinross, James, Nicholson, Jeremy, Takáts, Zoltán, Darzi, Ara and Mirnezami, Reza (2019) Network mapping of molecular biomarkers influencing radiation response in rectal cancer. Clinical Colorectal Cancer. (doi:10.1016/j.clcc.2019.01.004).

Record type: Review

Abstract

Preoperative radiotherapy (RT) plays an important role in the management of locally advanced rectal cancer (RC). Tumor regression after RT shows marked variability, and robust molecular methods are needed to help predict likely response. The aim of this study was to review the current published literature and use Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC. 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 nonsignificant results were included in the analysis. Significance was binarized on the basis of univariate 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 RC radiation response. Seventy-two individual biomarkers across 74 studies were identified. 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. Homogenizing biomarker data from original articles using controlled GO terminology demonstrated that cellular mechanisms of response to RT in RC—in particular the metabolic response to RT—may hold promise in developing radiotherapeutic biomarkers to help predict, and in the future modulate, radiation response.

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Accepted/In Press date: 23 January 2019
e-pub ahead of print date: 10 February 2019
Keywords: Neoadjuvant therapy, Radiation tolerance, Radiotherapy, Rectal neoplasms

Identifiers

Local EPrints ID: 429644
URI: http://eprints.soton.ac.uk/id/eprint/429644
ISSN: 1533-0028
PURE UUID: 0c6e4c88-854d-4a1c-b379-4bf77b42d654

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Date deposited: 03 Apr 2019 16:30
Last modified: 07 Oct 2020 00:15

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Contributors

Author: Liam Poynter
Author: Dieter Galea
Author: Kirill Veselkov
Author: James Kinross
Author: Jeremy Nicholson
Author: Zoltán Takáts
Author: Ara Darzi
Author: Reza Mirnezami

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