Identification of a Radiosensitivity Signature Using Integrative Metaanalysis of Published Microarray Data for NCI-60 Cancer Cells

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2012 Aug 1

PMID 22846430

Citations 81

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

Affiliations

Soon will be listed here.

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.

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References

Amundson S, Do K, Vinikoor L, Lee R, Koch-Paiz C, Ahn J . Integrating global gene expression and radiation survival parameters across the 60 cell lines of the National Cancer Institute Anticancer Drug Screen. Cancer Res. 2008; 68(2):415-24. DOI: 10.1158/0008-5472.CAN-07-2120. View

Park C, Zhang H, Yao E, Park C, Bissell M . Beta1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts. Cancer Res. 2008; 68(11):4398-405. PMC: 3719863. DOI: 10.1158/0008-5472.CAN-07-6390. View

Makrilia N, Kollias A, Manolopoulos L, Syrigos K . Cell adhesion molecules: role and clinical significance in cancer. Cancer Invest. 2009; 27(10):1023-37. DOI: 10.3109/07357900902769749. View

Shankavaram U, Reinhold W, Nishizuka S, Major S, Morita D, Chary K . Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study. Mol Cancer Ther. 2007; 6(3):820-32. DOI: 10.1158/1535-7163.MCT-06-0650. View

Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T, Kazama Y, Tanaka J . Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res. 2006; 66(7):3370-4. DOI: 10.1158/0008-5472.CAN-05-3834. View

Hirst D, Robson T . Molecular biology: the key to personalised treatment in radiation oncology?. Br J Radiol. 2010; 83(993):723-8. PMC: 3473406. DOI: 10.1259/bjr/91488645. View

Xia F, Powell S . The molecular basis of radiosensitivity and chemosensitivity in the treatment of breast cancer. Semin Radiat Oncol. 2002; 12(4):296-304. DOI: 10.1053/srao.2002.35250. View

Goeman J, van de Geer S, de Kort F, van Houwelingen H . A global test for groups of genes: testing association with a clinical outcome. Bioinformatics. 2003; 20(1):93-9. DOI: 10.1093/bioinformatics/btg382. View

Tusher V, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-21. PMC: 33173. DOI: 10.1073/pnas.091062498. View

10.

Begg A . Predicting response to radiotherapy: evolutions and revolutions. Int J Radiat Biol. 2009; 85(10):825-36. View

11.

Fukuda K, Sakakura C, Miyagawa K, Kuriu Y, Kin S, Nakase Y . Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradiation. Br J Cancer. 2004; 91(8):1543-50. PMC: 2409931. DOI: 10.1038/sj.bjc.6602187. View

12.

Rescher U, Gerke V . Annexins--unique membrane binding proteins with diverse functions. J Cell Sci. 2004; 117(Pt 13):2631-9. DOI: 10.1242/jcs.01245. View

13.

Ross D, Scherf U, Eisen M, Perou C, Rees C, Spellman P . Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet. 2000; 24(3):227-35. DOI: 10.1038/73432. View

14.

Harima Y, Ikeda K, Utsunomiya K, Shiga T, Komemushi A, Kojima H . Identification of genes associated with progression and metastasis of advanced cervical cancers after radiotherapy by cDNA microarray analysis. Int J Radiat Oncol Biol Phys. 2009; 75(4):1232-9. DOI: 10.1016/j.ijrobp.2009.07.002. View

15.

Ogawa K, Murayama S, Mori M . Predicting the tumor response to radiotherapy using microarray analysis (Review). Oncol Rep. 2007; 18(5):1243-8. View

16.

Sandfort V, Koch U, Cordes N . Cell adhesion-mediated radioresistance revisited. Int J Radiat Biol. 2007; 83(11-12):727-32. DOI: 10.1080/09553000701694335. View

17.

Nam J, Chung Y, Hsu H, Park C . beta1 integrin targeting to enhance radiation therapy. Int J Radiat Biol. 2009; 85(11):923-8. DOI: 10.3109/09553000903232876. View

18.

Vocca I, Franco P, Alfano D, Votta G, Carriero M, Estrada Y . Inhibition of migration and invasion of carcinoma cells by urokinase-derived antagonists of alphavbeta5 integrin activation. Int J Cancer. 2008; 124(2):316-25. DOI: 10.1002/ijc.23933. View

19.

Jirawatnotai S, Hu Y, Michowski W, Elias J, Becks L, Bienvenu F . A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. 2011; 474(7350):230-4. PMC: 3134411. DOI: 10.1038/nature10155. View

20.

Torres-Roca J, Eschrich S, Zhao H, Bloom G, Sung J, McCarthy S . Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005; 65(16):7169-76. DOI: 10.1158/0008-5472.CAN-05-0656. View