Transcript Comprehensive Gene Expression Analysis of

Comprehensive Gene Expression Analysis of
Prostate Cancer Reveals Distinct
Transcriptional Programs Associated With
Metastatic Disease
Eva, La Tullippe, Jaya Satagopan, Alex Smith, Howard Scher,
Peter Scardino, Victor Reuter, William Gerald.
Department of Pathology
Kevin Paiz-Ramirez
Janelle N. Ruiz
Biology 398.01
Department of Biology
Loyola Marymount University
April 11, 2010
Outline
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Differences in gene expression profiles between
progressive and non-progressive tumors can explain
the mechanism of disease.
Microarray analysis was used to determine differential
gene expression
Differentially expressed genes between metastatic and
primary tumors were found:
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Cell Cycle Regulation
Mitosis
Signaling
DNA Replication
Metastatic tumors had higher proliferation index than
primary tumors.
Both previously-identified and novel differentially
expressed genes were identified.
Importance of Investigating Gene Expression
Profiles of Prostate Cancer Tumors
• Carcinoma of the prostate is the most common
cancer in the United States
• Tumors can be classified as being either
metastasized or localized
• Development of metastatic disease leads to death.
• Improving tumor classification and therapy can be
achieved by identifying
– Genes
– Gene expression profiles
– Biological pathways
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
• Analysis was preformed with Affymetrix chips
• Within chip and between chip normalization was
carried out by multiplying expression values such that
the average expression was 2500
• They considered genes to be differentially expressed if
they differed by 3 fold between two groups
• They took the Log10 of the ratio of the means.
Differences in Clinical and Pathological Features
Between Primary and Metastatic Tumors
Clustering Shows That Primary Tumors Have A
Different Expression Profile Than The
Metastatic Tumors
Genes Involved in Cell Cycle Regulation, DNA
Replication and Repair, and Mitosis Were Highly
Differentially Expressed in Metastatic Tumors
Genes Involved in Signaling and Signal
Transduction Were Differentially Expressed in
Metastatic Tumors
Genes Involved in Transcriptional Regulation and Cell
Adhesion Were Highly Differentially Expressed in
Metastatic Tumors
Metastatic Tumors Present Higher Proliferation
Index Than Primary Tumors
Metastatic Tumors Present Higher Proliferation
Index Than Primary Tumors
Quantitative RT-PCR Confirms Relative Expression
Values Observed From Microarray Experiment
Microarray Data Reveals Both Previously-Identified
and Novel Differentially Expressed Genes Between
Primary and Metastatic Tumors
• Previous studies have revealed similar patterns of gene
expression.
• Differentially expressed genes of functional pathways
previously implicated in aggressive disease
• Analysis reveled hundreds of poorly characterized gene
clusters that likely represent novel genes of unknown
function
– Biological activity of these genes can be inferred from
other known genes with shared expression patterns
Determining Function of Unknown Genes May
Identify Potential Therapeutic Targets
• Few prior studies have used high-throughput gene
expression analysis to study prostate cancer
metastasis
• Some of genes differentially expressed may identity
critical functional pathways:
– Example: MYBL2 may signify critical component
of cell cycle regulation in metastatic cancer
• Further studies would determine the function of
unknown genes and identify potential therapeutic
targets for treatment.
References
• LaTulippe E, Satagopan J, Smith A, Scher H,
Scardino P, Reuter V, and Gerald L. Comprehensive
gene expression analysis of prostate cancer reveals
distinct transcriptional programs associated with
metastatic disease. Cancer Res 2002 Aug 1; 62(15)
4499-506.