Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification
| Autor: | Anne-Marie O'Farrell, Samuel Deprimo, Lily Wong, Deepak B. Khatry, William C. Manning, Beverly D. Smolich, Susan L Nicholas, Julie M. Cherrington |
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| Jazyk: | angličtina |
| Předmět: |
Oncology
Male medicine.medical_specialty Cancer Research Indoles Microarray Colorectal cancer Angiogenesis Inhibitors lcsh:RC254-282 Peripheral blood mononuclear cell chemistry.chemical_compound Antigens CD Predictive Value of Tests Internal medicine Biomarkers Tumor Genetics Medicine Humans Pyrroles Neoplasm Metastasis Aged Oligonucleotide Array Sequence Analysis Membrane Glycoproteins business.industry Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling CD24 Antigen Middle Aged Protein-Tyrosine Kinases lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Gene expression profiling Clinical trial Vascular endothelial growth factor Gene Expression Regulation Neoplastic Lactoferrin chemistry Clinical Trials Phase III as Topic Matrix Metalloproteinase 9 Immunology Leukocytes Mononuclear Biomarker (medicine) Female DNA microarray business Colorectal Neoplasms Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 3, Iss 1, p 3 (2003) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-3-3 |
| Popis: | Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies. |
| Databáze: | OpenAIRE |
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