Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines

被引:675
作者
Geeleher, Paul [1 ]
Cox, Nancy J. [2 ]
Huang, R. Stephanie [1 ]
机构
[1] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA
[2] Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL 60637 USA
基金
美国国家卫生研究院; 英国惠康基金;
关键词
GROWTH-FACTOR RECEPTOR; LUNG-CANCER; MOLECULAR CLASSIFICATION; MUTATIONS; SURVIVAL; REPRODUCIBILITY; NORMALIZATION; REGRESSION; SIGNATURE; SUBTYPES;
D O I
10.1186/gb-2014-15-3-r47
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We demonstrate a method for the prediction of chemotherapeutic response in patients using only before-treatment baseline tumor gene expression data. First, we fitted models for whole-genome gene expression against drug sensitivity in a large panel of cell lines, using a method that allows every gene to influence the prediction. Following data homogenization and filtering, these models were applied to baseline expression levels from primary tumor biopsies, yielding an in vivo drug sensitivity prediction. We validated this approach in three independent clinical trial datasets, and obtained predictions equally good, or better than, gene signatures derived directly from clinical data.
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页数:12
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