Gene expression profiling as a tool for basic analysis and clinical application of human cancer

The sequentiation of the human genome, together with the development of high throughput technologies, particularly gene‐expression profiling, is giving us the opportunity to describe biological features in a quantitative manner. Here we review the use of global gene expression analyses in cancer research. Microarray analyses of tumor samples have allowed researchers the development of profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome, or the response to therapy. Profiling of experimental models with activation of certain oncogenic pathways could also be used to ascertain the molecular events involved in the establishment and development of tumors and, consequently, these models could be validated as tools for preclinical therapy. Furthermore, the detailed analysis of gene expression deregulation after response to the therapies in such models would allow us to predict the response to specific drugs, and to target the therapies to patients in search for individualized management of the disease. © 2008 Wiley‐Liss, Inc.

[1]  M. Cronin,et al.  A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. , 2004, The New England journal of medicine.

[2]  J. Nevins,et al.  Mining gene expression profiles: expression signatures as cancer phenotypes , 2007, Nature Reviews Genetics.

[3]  H. Dressman,et al.  Genomic signatures to guide the use of chemotherapeutics , 2006, Nature Medicine.

[4]  Yi Zhang,et al.  Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. , 2006, Cancer research.

[5]  P. Meltzer,et al.  Gene expression profiling of human sarcomas: insights into sarcoma biology. , 2005, Cancer research.

[6]  M. Newton,et al.  Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers. , 2007, Cancer research.

[7]  Yudong D. He,et al.  A Gene-Expression Signature as a Predictor of Survival in Breast Cancer , 2002 .

[8]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Nobel,et al.  Concordance among Gene-Expression – Based Predictors for Breast Cancer , 2011 .

[10]  J. Mesirov,et al.  An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis , 2005, Nature Genetics.

[11]  C. Sotiriou,et al.  Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? , 2007, Nature Reviews Cancer.

[12]  M Vingron,et al.  Identification and Classification of Differentially Expressed Genes in Renal Cell Carcinoma by Expression Profiling on a Global Human 31 , 500-Element cDNA Array , 2001 .

[13]  S. Thorgeirsson,et al.  Application of comparative functional genomics to identify best-fit mouse models to study human cancer , 2004, Nature Genetics.

[14]  J. Downing,et al.  Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. , 2002, Cancer cell.

[15]  David E. Misek,et al.  Gene-expression profiles predict survival of patients with lung adenocarcinoma , 2002, Nature Medicine.

[16]  A. Nobel,et al.  The molecular portraits of breast tumors are conserved across microarray platforms , 2006, BMC Genomics.

[17]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

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

[19]  Richard Simon,et al.  Molecular diagnosis of Burkitt's lymphoma. , 2006, The New England journal of medicine.

[20]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[21]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[22]  D. Botstein,et al.  Diversity of gene expression in adenocarcinoma of the lung , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T. Poggio,et al.  Prediction of central nervous system embryonal tumour outcome based on gene expression , 2002, Nature.

[24]  U. Alon,et al.  Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Jeffrey T. Chang,et al.  Oncogenic pathway signatures in human cancers as a guide to targeted therapies , 2006, Nature.

[26]  Stefano Monti,et al.  Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  S. Mukherjee,et al.  A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. , 2006, The New England journal of medicine.

[28]  S. Dhanasekaran,et al.  Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. , 2007, Cancer cell.

[29]  P. Dennis,et al.  An overview of lung cancer genomics and proteomics. , 2005, American journal of respiratory cell and molecular biology.

[30]  E. Lander,et al.  Gene expression correlates of clinical prostate cancer behavior. , 2002, Cancer cell.

[31]  T. Graeber,et al.  Myc-driven murine prostate cancer shares molecular features with human prostate tumors. , 2003, Cancer cell.

[32]  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.

[33]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[34]  Kathleen R. Cho,et al.  Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. , 2002, Cancer research.

[35]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.