Towards Improved Cancer Diagnosis and Prognosis Using Analysis of Gene Expression Data and Computer Aided Imaging

With the increasing cost effectiveness of whole slide digital scanners, gene expression microarray and SNP technologies, tissue specimens can now be analyzed using sophisticated computer aided image and data analysis techniques for accurate diagnoses and identification of prognostic markers and potential targets for therapeutic intervention. Microarray analysis is routinely able to identify biomarkers correlated with survival and reveal pathways underlying pathogenesis and invasion. In this paper we describe how microarray profiling of tumor samples combined with simple but powerful methods of analysis can identify biologically distinct disease subclasses of breast cancer with distinct molecular signatures, differential recurrence rates and potentially, very different response to therapy. Image analysis methods are also rapidly finding application in the clinic, complementing the pathologist in quantitative, reproducible, detection, staging, and grading of disease. We will describe novel computerized image analysis techniques and machine learning tools for automated cancer detection from digitized histopathology and how they can be employed for disease diagnosis and prognosis for prostate and breast cancer.

[1]  Yoav Freund,et al.  Experiments with a New Boosting Algorithm , 1996, ICML.

[2]  George Lee,et al.  An Empirical Comparison of Dimensionality Reduction Methods for Classifying Gene and Protein Expression Datasets , 2007, ISBRA.

[3]  C. DeLisi,et al.  Data Perturbation Independent Diagnosis and Validation of Breast Cancer Subtypes Using Clustering and Patterns , 2006, Cancer informatics.

[4]  Debajit K. Biswas,et al.  NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis , 2004 .

[5]  S. Bailey,et al.  Nuclear factor-κB activation: a molecular therapeutic target for estrogen receptor–negative and epidermal growth factor receptor family receptor–positive human breast cancer , 2007, Molecular Cancer Therapeutics.

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

[7]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Sheaff,et al.  The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators. , 2003, Surgery.

[9]  Andrew Zisserman,et al.  A Statistical Approach to Texture Classification from Single Images , 2004, International Journal of Computer Vision.

[10]  E. Winer,et al.  Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer , 2007, Clinical Cancer Research.

[11]  Jill P. Mesirov,et al.  Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data , 2003, Machine Learning.

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

[13]  Adrian E. Raftery,et al.  Model-Based Clustering, Discriminant Analysis, and Density Estimation , 2002 .

[14]  Z. Trajanoski,et al.  Effector memory T cells, early metastasis, and survival in colorectal cancer. , 2005, The New England journal of medicine.

[15]  Peter L. Hammer,et al.  Spanned patterns for the logical analysis of data , 2006, Discret. Appl. Math..

[16]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[17]  Shridar Ganesan,et al.  X chromosomal abnormalities in basal-like human breast cancer. , 2006, Cancer cell.

[18]  S. Hilsenbeck,et al.  Neoadjuvant trastuzumab induces apoptosis in primary breast cancers , 2005, Nature Clinical Practice Oncology.

[19]  S. Ménard,et al.  Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  Vipin Kumar,et al.  Multilevel Graph Partitioning Schemes , 1995, ICPP.

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

[22]  Student,et al.  THE PROBABLE ERROR OF A MEAN , 1908 .

[23]  Luis Mateus Rocha,et al.  Singular value decomposition and principal component analysis , 2003 .

[24]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[25]  G. Dranoff The Therapeutic Implications of Intratumoral Regulatory T Cells , 2005, Clinical Cancer Research.

[26]  S. Bailey,et al.  Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer. , 2007, Molecular cancer therapeutics.

[27]  Joydeep Ghosh,et al.  Cluster Ensembles --- A Knowledge Reuse Framework for Combining Multiple Partitions , 2002, J. Mach. Learn. Res..

[28]  Wolfgang Heller,et al.  Triple-negative breast cancer: therapeutic options. , 2007, The Lancet. Oncology.

[29]  L. Happerfield,et al.  Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast. , 1996, British Journal of Cancer.

[30]  Yi Zhang,et al.  Entropy-based subspace clustering for mining numerical data , 1999, KDD '99.

[31]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Lisa A Carey,et al.  Gene expression profiling in breast cancer , 2007, Current opinion in oncology.

[33]  Philip M. Long,et al.  Breast cancer classification and prognosis based on gene expression profiles from a population-based study , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Anant Madabhushi,et al.  AUTOMATED GRADING OF PROSTATE CANCER USING ARCHITECTURAL AND TEXTURAL IMAGE FEATURES , 2007, 2007 4th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[35]  R. Salunga,et al.  Gene expression profiles of human breast cancer progression , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  D. Vigushin,et al.  Gene-expression profiling and identification of patients at high risk of breast cancer , 2002, The Lancet.

[37]  S. Ménard,et al.  Prognostic significance of her‐2/neu expression in breast cancer and its relationship to other prognostic factors , 1991, International journal of cancer.

[38]  Ali S. Hadi,et al.  Finding Groups in Data: An Introduction to Chster Analysis , 1991 .

[39]  C. Sotiriou,et al.  Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer , 2002, Breast Cancer Research.

[40]  J. Anim,et al.  Relationship between the expression of various markers and prognostic factors in breast cancer. , 2005, Acta histochemica.

[41]  J. Foekens,et al.  Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer , 2005, The Lancet.

[42]  Robert Tibshirani,et al.  Estimating the number of clusters in a data set via the gap statistic , 2000 .

[43]  R. Dutton,et al.  Type 1 and type 2 tumor infiltrating effector cell subpopulations in progressive breast cancer. , 2004, Clinical immunology.

[44]  Sankar Ghosh,et al.  NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[45]  János Szöllosi,et al.  Epidermal growth factor receptor coexpression modulates susceptibility to Herceptin in HER2/neu overexpressing breast cancer cells via specific erbB-receptor interaction and activation. , 2005, Experimental cell research.

[46]  M. Hussein,et al.  Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations , 2006, Journal of Clinical Pathology.

[47]  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.

[48]  G. Bhanot,et al.  Manifold learning with graph-based features for identifying extent of lymphocytic infiltration from high grade , HER 2 + breast cancer histology , 2008 .

[49]  H. Fiegl,et al.  The Expression of the Regulatory T Cell–Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer , 2005, Clinical Cancer Research.

[50]  Gabriela Alexe,et al.  High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates. , 2007, Cancer research.

[51]  Joydeep Ghosh,et al.  Cluster Ensembles A Knowledge Reuse Framework for Combining Partitionings , 2002, AAAI/IAAI.

[52]  Purang Abolmaesumi,et al.  Detection of Prostate Cancer from Whole-Mount Histology Images Using Markov Random Fields , 2008 .

[53]  Anant Madabhushi,et al.  A Boosting Cascade for Automated Detection of Prostate Cancer from Digitized Histology , 2006, MICCAI.

[54]  Z. Trajanoski,et al.  Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome , 2006, Science.

[55]  L. Egevad,et al.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma , 2005, The American journal of surgical pathology.

[56]  J. Dering,et al.  Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro , 2007, Breast Cancer Research and Treatment.

[57]  Teuvo Kohonen,et al.  Self-Organizing Maps , 2010 .

[58]  S. Ménard,et al.  Pilot Study of the Mechanism of Action of Preoperative Trastuzumab in Patients with Primary Operable Breast Tumors Overexpressing HER2 , 2004, Clinical Cancer Research.

[59]  Charles M Perou,et al.  EGFR associated expression profiles vary with breast tumor subtype , 2007, BMC Genomics.

[60]  Ferran Algaba,et al.  Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies , 2005, BJU international.

[61]  Donald Geman,et al.  Stochastic Relaxation, Gibbs Distributions, and the Bayesian Restoration of Images , 1984, IEEE Transactions on Pattern Analysis and Machine Intelligence.

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

[63]  F. Bertucci,et al.  Gene-expression profiling and identification of patients at high risk of breast cancer , 2002, The Lancet.

[64]  Donald Geman,et al.  Stochastic relaxation, Gibbs distributions, and the Bayesian restoration of images , 1984 .

[65]  James Kelly,et al.  AutoClass: A Bayesian Classification System , 1993, ML.

[66]  Jill P. Mesirov,et al.  Portraits of breast cancer progression , 2007, BMC Bioinformatics.

[67]  Anant Madabhushi,et al.  Automated grading of breast cancer histopathology using spectral clustering with textural and architectural image features , 2008, 2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[68]  Carsten O. Peterson,et al.  Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. , 2001, Cancer research.

[69]  Joshy George,et al.  Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. , 2006, Cancer research.

[70]  V. Beral Breast cancer and hormone replacement therapy (HRT): collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer , 2002, Breast Cancer Research.

[71]  D. Laune,et al.  Oestrogen receptor negative breast cancers exhibit high cytokine content , 2007, Breast Cancer Research.

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

[73]  Eric S. Lander,et al.  Integrative Genomic Approaches Identify IKBKE as a Breast Cancer Oncogene , 2007, Cell.

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

[75]  Michael J. Becich,et al.  Tests for finding complex patterns of differential expression in cancers: towards individualized medicine , 2004, BMC Bioinformatics.

[76]  T. Sørlie,et al.  Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms , 2006, BMC Genomics.

[77]  J. Blay,et al.  Dendritic Cell Infiltration and Prognosis of Early Stage Breast Cancer , 2004, Clinical Cancer Research.

[78]  L. Happerfield,et al.  Angiogenesis and inflammation in ductal carcinoma in situ of the breast , 1997, The Journal of pathology.