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Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of
Marc E Lenburg1, Louis S Liou, Norman P Gerry
1Department of Genetics & Genomics, Boston University School of Medicine 715 Albany Street, E613 Boston, Massachusetts 02118, USA. mlenburg@bu.edu
BMC Cancer
|December 3, 2003
Summary
This study identifies new genes involved in renal cell carcinoma (kidney cancer) by analyzing gene expression data. Rigorous methods improve accuracy, revealing potential oncogenes and tumor suppressors for better cancer treatment strategies.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Renal cell carcinoma (RCC) is a prevalent cancer often presenting with metastatic disease and lacking effective treatments.
- Genome-wide expression profiling studies for RCC have shown poor agreement on differentially regulated genes.
- Understanding these discrepancies is crucial for advancing RCC research and therapeutic development.
Purpose of the Study:
- To profile renal cell tumor gene expression using genome-wide microarrays.
- To compare the current analysis with previous microarray studies to understand discrepancies.
- To identify novel differentially expressed genes in RCC.
Main Methods:
- Hybridized total RNA from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays.
- Removed technically defective samples and unreliable probesets.
- Detected differential gene expression using parametric methods and identified overrepresented keywords with the Fisher-exact test.
Main Results:
- Identified 1,234 genes with >3-fold change in renal tumors; 800 were newly reported.
- Found 33 of 37 (89%) differentially expressed genes common to at least three previous studies.
- Demonstrated that filtering defective samples and unreliable genes enhances analysis sensitivity and power.
Conclusions:
- Poor overlap in previous studies is likely due to sample-wise voting schemes without false positive control.
- Identified novel oncogenes and tumor suppressor genes crucial for renal cell carcinogenesis.
- Emphasizes the necessity of rigorous statistical approaches in microarray studies for reliable results.