The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform
Open accessAbstract
Purpose The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials Radiosensitivity, as represented by the Survival Fraction at 2 Gy (SF2) was modeled in 48 human cancer cell lines. We apply a linear regression algorithm that integrates gene expression with biological variables including: ras status (mut/wt), tissue of origin (TO) and p53 status (mut/wt). Results The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression. This network was reduced to a 10-hub network that includes: c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1 and IRF1. Nine targets associated with radiosensitization drugs link to the network, demonstrating clinical relevance. Furthermore, the model identifies four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis along with TO and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included: DNA repair, cell cycle, apoptosis and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon and breast cancers. Conclusions We developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We propose this platform will play a central role in the integration of biology into clinical radiation oncology practice.
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Scott, J. G., Sedor, G., Ellsworth, P., Scarborough, J. A., Ahmed, K. A., Oliver, D. E., Eschrich, S. A., Kattan, M. W., & Torres-Roca, J. F. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00347-8 · Cited by 158
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Metadata
- Authors
- Eschrich, S., Zhang, H., Zhao, H., Boulware, D., Lee, J.-H., Bloom, G., & Torres-Roca, J. F.
- Venue
- International Journal of Radiation Oncology*Biology*Physics
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 75
- Issue
- 2
- Pages
- 497-505
- ISSN
- 0360-3016 (ISSN-L)
- OpenAlex
- W2050034556
- Cited by
- 276
- References
- 46
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
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