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[Cancer Research 62, 4499-4506, August 1, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

Comprehensive Gene Expression Analysis of Prostate Cancer Reveals Distinct Transcriptional Programs Associated with Metastatic Disease1

Eva LaTulippe, Jaya Satagopan, Alex Smith, Howard Scher, Peter Scardino, Victor Reuter and William L. Gerald2

Departments of Pathology [E. L., V. R., W. L. G.], Epidemiology and Biostatistics [J. S., A. S.], Urology [P. S.], and Genitourinary Oncology Service, Department of Medicine [H. S.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and Department of Medicine, Joan and Sanford I. Weill College of Medicine of Cornell University, New York, New York 10021 [H. S.]

The identification of genes that contribute to the biological basis for clinical heterogeneity and progression of prostate cancer is critical to accurate classification and appropriate therapy. We performed a comprehensive gene expression analysis of prostate cancer using oligonucleotide arrays with 63,175 probe sets to identify genes and expressed sequences with strong and uniform differential expression between nonrecurrent primary prostate cancers and metastatic prostate cancers. The mean expression value for >3,000 tumor-intrinsic genes differed by at least 3-fold between the two groups. This includes many novel ESTs not previously implicated in prostate cancer progression. Many differentially expressed genes participate in biological processes that may contribute to the clinical phenotype. One example was a strong correlation between high proliferation rates in metastatic cancers and overexpression of genes that participate in cell cycle regulation, DNA replication, and DNA repair. Other functional categories of differentially expressed genes included transcriptional regulation, signaling, signal transduction, cell structure, and motility. These differentially expressed genes reflect critical cellular activities that contribute to clinical heterogeneity and provide diagnostic and therapeutic targets.




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