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The tissue micro-array as a translational research tool for biomarker profiling and validation
1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA. dseligson@mednet.ucla.edu
Summary
Tissue micro-arrays (TMAs) are crucial for biomarker validation. In renal cell carcinoma (RCC), Epithelial Protein Cell Adhesion Molecule (EpCAM) showed prognostic value but poor immunotherapy targeting due to low expression, halting clinical trials.
Area of Science:
- Translational research
- Biomarker discovery
- Oncology
Background:
- High-throughput molecular technologies generate numerous potential biomarkers.
- Target validation necessitates well-characterized tissue resources and clinical data.
- Tissue micro-arrays (TMAs) are increasingly vital for biomarker discovery and validation.
Purpose of the Study:
- To describe the utility of TMAs in biomarker profiling for translational research.
- To investigate Epithelial Protein Cell Adhesion Molecule (EpCAM) as a biomarker in renal cell carcinoma (RCC).
Main Methods:
- Utilized TMAs for in situ gene expression analysis across numerous tissue samples.
- Examined EpCAM expression and its correlation with survival in 318 clear cell RCC patients.
- Performed Cox proportional hazards multivariate analysis to assess prognostic significance.
Main Results:
- EpCAM was identified as an independent prognosticator for improved disease-specific survival in clear cell RCC (HR 0.63, p=0.017).
- EpCAM expression was infrequent in clear cell RCC, contrary to its typical widespread epithelial expression.
- This finding indicated EpCAM is a poor target for immunotherapy in this cancer type.
Conclusions:
- TMAs are effective tools for biomarker profiling and translational research.
- EpCAM's low expression in clear cell RCC suggests it is unsuitable for immunotherapy targeting.
- The TMA study provided evidence to halt costly and lengthy clinical trials for EpCAM-based immunotherapy in RCC.