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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
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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:
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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:
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Nucleosome activity
Chromatin activity
Chromosomal activity
DNA packaging
• Increases centered on:
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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:
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–
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Mitosis
Spindle organization
Chromosome segregation
DNA replication
• Decreases centered on:
– Muscle contraction
– Chromatin remodeling complex
– Oxidoreductase activity