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

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.

[1]  I. Jolliffe A Note on the Use of Principal Components in Regression , 1982 .

[2]  R. Tibshirani Regression Shrinkage and Selection via the Lasso , 1996 .

[3]  S. Jagannath,et al.  CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION , 1998, British journal of haematology.

[4]  R. Wooster The cancer genome project , 2002 .

[5]  Friedrich Leisch,et al.  Sweave: Dynamic Generation of Statistical Reports Using Literate Data Analysis , 2002, COMPSTAT.

[6]  R. Tibshirani,et al.  Diagnosis of multiple cancer types by shrunken centroids of gene expression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Van,et al.  A gene-expression signature as a predictor of survival in breast cancer. , 2002, The New England journal of medicine.

[8]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[9]  Syed Mohsin,et al.  Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer , 2003, The Lancet.

[10]  Adrian Wiestner,et al.  A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[12]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[13]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[14]  Benjamin M. Bolstad,et al.  affy - analysis of Affymetrix GeneChip data at the probe level , 2004, Bioinform..

[15]  R. Tibshirani,et al.  Gene expression profiling identifies clinically relevant subtypes of prostate cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Thomas Lengauer,et al.  ROCR: visualizing classifier performance in R , 2005, Bioinform..

[17]  M. Ostland,et al.  Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  R. Myers,et al.  Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data , 2005, Nucleic acids research.

[19]  S. Bicciato,et al.  Molecular classification of multiple myeloma: a distinct transcriptional profile characterizes patients expressing CCND1 and negative for 14q32 translocations. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  H. Zou,et al.  Regularization and variable selection via the elastic net , 2005 .

[21]  Daniel Birnbaum,et al.  Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. , 2005, Cancer research.

[22]  John Crowley,et al.  The molecular classification of multiple myeloma. , 2006, Blood.

[23]  M. J. van de Vijver,et al.  Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. , 2006, Journal of the National Cancer Institute.

[24]  Maqc Consortium The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements , 2006, Nature Biotechnology.

[25]  Douglas G Altman,et al.  Dichotomizing continuous predictors in multiple regression: a bad idea , 2006, Statistics in medicine.

[26]  Tom Fawcett,et al.  ROC Graphs: Notes and Practical Considerations for Researchers , 2007 .

[27]  Arnoldo Frigessi,et al.  BIOINFORMATICS ORIGINAL PAPER doi:10.1093/bioinformatics/btm305 Gene expression Predicting survival from microarray data—a comparative study , 2022 .

[28]  Anthony Boral,et al.  Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. , 2006, Blood.

[29]  Sean R. Davis,et al.  GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor , 2007, Bioinform..

[30]  C. Sawyers The cancer biomarker problem , 2008, Nature.

[31]  Sang Hong Lee,et al.  Predicting Unobserved Phenotypes for Complex Traits from Whole-Genome SNP Data , 2008, PLoS genetics.

[32]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[33]  Anne-Laure Boulesteix,et al.  Survival prediction using gene expression data: A review and comparison , 2009, Comput. Stat. Data Anal..

[34]  Z. Szallasi,et al.  Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  Yuqiu Jiang,et al.  Personalized medicine in oncology: tailoring the right drug to the right patient. , 2010, Biomarkers in medicine.

[36]  Mukesh Verma,et al.  Cancer Biomarkers: Are We Ready for the Prime Time? , 2010, Cancers.

[37]  Chia Huey Ooi,et al.  Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. , 2011, Gastroenterology.

[38]  Faramarz Valafar,et al.  Empirical comparison of cross-platform normalization methods for gene expression data , 2011, BMC Bioinformatics.

[39]  R. Tibshirani,et al.  Regression shrinkage and selection via the lasso: a retrospective , 2011 .

[40]  Edward S. Kim,et al.  The BATTLE trial: personalizing therapy for lung cancer. , 2011, Cancer discovery.

[41]  Rafael Sirera,et al.  The Role of Tumor Stroma in Cancer Progression and Prognosis: Emphasis on Carcinoma-Associated Fibroblasts and Non-small Cell Lung Cancer , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[42]  S. Ramaswamy,et al.  Systematic identification of genomic markers of drug sensitivity in cancer cells , 2012, Nature.

[43]  Adam A. Margolin,et al.  The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity , 2012, Nature.

[44]  Michael Peyton,et al.  An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance , 2012, Clinical Cancer Research.

[45]  Daniel Gianola,et al.  Using Whole-Genome Sequence Data to Predict Quantitative Trait Phenotypes in Drosophila melanogaster , 2012, PLoS genetics.

[46]  Maqc Consortium The MicroArray Quality Control ( MAQC )-II study of common practices for the development and validation of microarray-based predictive models , 2012 .

[47]  Mira Ayadi,et al.  Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value , 2013, PLoS medicine.

[48]  Julio Saez-Rodriguez,et al.  Machine Learning Prediction of Cancer Cell Sensitivity to Drugs Based on Genomic and Chemical Properties , 2012, PloS one.

[49]  Xiao Xu,et al.  Parallel comparison of Illumina RNA-Seq and Affymetrix microarray platforms on transcriptomic profiles generated from 5-aza-deoxy-cytidine treated HT-29 colon cancer cells and simulated datasets , 2013, BMC Bioinformatics.

[50]  Jay Shendure,et al.  The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line , 2013, Nature.

[51]  Erika Cule,et al.  Ridge Regression in Prediction Problems: Automatic Choice of the Ridge Parameter , 2013, Genetic epidemiology.

[52]  Richard Simon,et al.  Implementing personalized cancer genomics in clinical trials , 2013, Nature Reviews Drug Discovery.

[53]  Cynthia H Zhang,et al.  Maximizing the commercial value of personalized therapeutics and companion diagnostics , 2013, Nature Biotechnology.

[54]  Jeroen F. J. Laros,et al.  Reproducibility of high-throughput mRNA and small RNA sequencing across laboratories , 2013, Nature Biotechnology.

[55]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[56]  Hae Kyung Im,et al.  Poly‐Omic Prediction of Complex Traits: OmicKriging , 2013, Genetic epidemiology.

[57]  R. S. Huang,et al.  Abstract 5561: Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines , 2014 .