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Identification of a radiosensitivity signature using integrative metaanalysis of published microarray data for NCI-60 cancer cells.

Authors
 Han Sang Kim  ;  Sang Cheol Kim  ;  Sun Jeong Kim  ;  Chan Hee Park  ;  Hei-Cheul Jeung  ;  Yong Bae Kim  ;  Joong Bae Ahn  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 BMC Genomics, Vol.13 : 348, 2012 
Journal Title
 BMC Genomics 
ISSN
 1471-2164 
Issue Date
2012
Abstract
BACKGROUND: In the postgenome era, a prediction of response to treatment could lead to better dose selection for patients in radiotherapy. To identify a radiosensitive gene signature and elucidate related signaling pathways, four different microarray experiments were reanalyzed before radiotherapy. RESULTS: Radiosensitivity profiling data using clonogenic assay and gene expression profiling data from four published microarray platforms applied to NCI-60 cancer cell panel were used. The survival fraction at 2 Gy (SF2, range from 0 to 1) was calculated as a measure of radiosensitivity and a linear regression model was applied to identify genes or a gene set with a correlation between expression and radiosensitivity (SF2). Radiosensitivity signature genes were identified using significant analysis of microarrays (SAM) and gene set analysis was performed using a global test using linear regression model. Using the radiation-related signaling pathway and identified genes, a genetic network was generated. According to SAM, 31 genes were identified as common to all the microarray platforms and therefore a common radiosensitivity signature. In gene set analysis, functions in the cell cycle, DNA replication, and cell junction, including adherence and gap junctions were related to radiosensitivity. The integrin, VEGF, MAPK, p53, JAK-STAT and Wnt signaling pathways were overrepresented in radiosensitivity. Significant genes including ACTN1, CCND1, HCLS1, ITGB5, PFN2, PTPRC, RAB13, and WAS, which are adhesion-related molecules that were identified by both SAM and gene set analysis, and showed interaction in the genetic network with the integrin signaling pathway. CONCLUSIONS: Integration of four different microarray experiments and gene selection using gene set analysis discovered possible target genes and pathways relevant to radiosensitivity. Our results suggested that the identified genes are candidates for radiosensitivity biomarkers and that integrin signaling via adhesion molecules could be a target for radiosensitization.
Files in This Item:
T201203660.pdf Download
DOI
10.1186/1471-2164-13-348
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Sun Jeong(김선정)
Kim, Yong Bae(김용배) ORCID logo https://orcid.org/0000-0001-7573-6862
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Chan Hee(박찬희)
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89782
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