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Transcript
Exploring Comprehensive Gene Expression Analysis of Prostate Cancer Reveals Distinct Transcriptional Programs Associated With Metastatic Disease Through GenMAPP & MappFinder LaTulippe Eva, Satagopan Jaya, Smith Alex, Scher Howard, Scardino Peter, Reuter Victor, and William G. Cancer Research 2002 Aug 1; 62, 4499-4506. Kevin Paiz-Ramirez Janelle N. Ruiz Biology 398.01 Department of Biology Loyola Marymount University April 21, 2010 Outline Previous Studies Explored Function of Unknown Genes May Identify Potential Therapeutic Targets • • • La Tullippe et at. used high-throughput gene expression analysis to study prostate cancer metastasis Differentially expressed genes between metastatic and primary tumors were found in: I. Cell Cycle Regulation II. Mitosis III. Signaling IV. DNA Replication Metastatic tumors had higher proliferation index than primary tumors. Genome Wide Expression Analysis of Primary and Metastatic Prostate Cancers • Tissues samples were taken from: – 3 Non cancerous Patients – 23 Primary Prostate Cancer Patients – 9 Metastatic Prostate cancer Patients • Collected as biopsies from 1993-1999 • Genes were considered to be differentially expressed if they differed by 3 fold between two groups Running GenMAPP & MAPPfinder • The Log2 of the ratio of the means was calculated: – – – – H vs PG fold Met vs PG Fold H vs Met Fold AI vs PG Fold • Number of errors 1793/11977 • Z score > 2 • PermuteP <0.05 Increased & Decreased Results of H vs. PG Fold Increase Decrease Increased and Decreased Results of H vs.PG Fold • Decreases centered on: – – – – Nucleosome activity Chromatin activity Chromosomal activity DNA packaging • Increases centered on: – – – – Activation of MAPK activity Leukocyte chemotaxis Metanephros development Immune response Increased & Decreased Results of Met vs. PG Fold Increased Decreased Increased and Decreased Results of Met vs.PG Fold • Increases centered on: – – – – Mitosis Spindle organization Chromosome segregation DNA replication • Decreases centered on: – Muscle contraction – Chromatin remodeling complex – Oxidoreductase activity
