Predicting prostate cancer behavior using transcript profiles.

PURPOSE Prostate cancer represents a disease with diverse clinical outcomes. Treatment strategies that optimize benefit and minimize morbidities depend on accurate estimates of disease status and likelihood of progression. Emerging technologies capable of qualitatively and quantitatively profiling genes expressed by neoplastic tissues may provide insights into tumor behavior. This review discusses the use of microarray based transcript expression profiling to stratify human cancers into risk categories. MATERIALS AND METHODS MEDLINE was used to perform a comprehensive literature review of reports describing the assessment of gene expression profiles in malignant diseases. Particular emphasis was placed on studies developing models using individual genes or gene cohorts as predictors of prostate cancer outcome. RESULTS Alterations in the expression of individual genes identified by microarray analyses have been used in studies of outcome in cancers of the prostate and other tissue types. Profiles of expressed genes have been used to develop prediction models that stratify cancers into prognostic categories based on relapse rates or responses to therapy. CONCLUSIONS Gene expression profiles offer an opportunity for acquiring molecular determinants correlating with clinical outcome. With rare exceptions these profiles have yet to be validated or used in prospective studies. Future research will benefit from assessments of intratumor heterogeneity and host factors such as the immune response and hormonal milieu. The prospective validation of predictive models will serve to prove usefulness in the clinical arena.

[1]  T. Stamey,et al.  Biological determinants of cancer progression in men with prostate cancer. , 1999, JAMA.

[2]  M. Bittner,et al.  Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. , 2001, Cancer research.

[3]  E. Latulippe,et al.  Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. , 2002, Cancer research.

[4]  E. Liu,et al.  Genetic background is an important determinant of metastatic potential , 2003, Nature Genetics.

[5]  A W Partin,et al.  Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. , 1997, JAMA.

[6]  K. Gish,et al.  Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. , 2003, Cancer research.

[7]  M. Rubin,et al.  Profiling and verification of gene expression patterns in normal and malignant human prostate tissues by cDNA microarray analysis. , 2001, Neoplasia.

[8]  Matthias Kretzler,et al.  Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue. , 2002, The American journal of pathology.

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

[10]  T. Stamey,et al.  Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia. , 2001, The Journal of urology.

[11]  D. Chan,et al.  Natural History of Progression After PSA Elevation Following Radical Prostatectomy , 1999 .

[12]  M W Kattan,et al.  Evaluation of a Nomogram used to predict the pathologic stage of clinically localized prostate carcinoma , 1997, Cancer.

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

[14]  Jeffrey A. Magee,et al.  Expression profiling reveals hepsin overexpression in prostate cancer. , 2001, Cancer research.

[15]  M. Kattan,et al.  Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  M. Kattan,et al.  A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. , 1998, Journal of the National Cancer Institute.

[17]  E. Lander,et al.  A molecular signature of metastasis in primary solid tumors , 2003, Nature Genetics.

[18]  J. Trent,et al.  Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis , 2002, The Prostate.

[19]  Yingdong Zhao,et al.  Molecular Differentiation of High- and Moderate-Grade Human Prostate Cancer by cDNA Microarray Analysis , 2003, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

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

[21]  David Handelsman,et al.  Identification of differentially expressed genes in organ‐confined prostate cancer by gene expression array , 2001, The Prostate.

[22]  S. Dhanasekaran,et al.  Delineation of prognostic biomarkers in prostate cancer , 2001, Nature.

[23]  T. Stamey,et al.  Prostate cancer is highly predictable: a prognostic equation based on all morphological variables in radical prostatectomy specimens. , 2000, The Journal of urology.

[24]  J. Welsh,et al.  Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. , 2001, Cancer research.

[25]  D. Chan,et al.  The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. , 1993, The Journal of urology.

[26]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[27]  J. Cheville,et al.  Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. , 2003, Cancer research.

[28]  J. Trachtenberg,et al.  Relapse and cure rates of prostate cancer patients after radical prostatectomy and 5 years of follow-up. , 2000, Clinical biochemistry.

[29]  Rajiv Dhir,et al.  Gene expression analysis of prostate cancers , 2002, Molecular carcinogenesis.

[30]  K. Buetow,et al.  Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression , 1998, International journal of cancer.