Abstract
Background: Metastatic renal cell carcinoma (mRCC) patients treated with anti-vascular endothelial growth factor (VEGF) therapies demonstrate promising outcomes but not all patients benefit. Factors that predict response remain to be elucidated. Patients and methods: Nephrectomy material from 37 patients with mRCC receiving bevacizumab ± erlotinib was used for protein and gene expression assessment. Protein lysates were subjected to reverse-phase protein array profiling. RNA extracts were used to carry out gene expression microarray-based profiling. Normalized protein and gene expression data were correlated with overall survival (OS) and progression-free survival (PFS) using univariate Cox hazard model and linear regression. Immunoblotting was carried out to validate the results. Results: High protein levels of AMP-activated protein kinase and low levels of cyclin B1 (CCNB1) were associated with longer OS and PFS. Further validation revealed reduced expression and activation of phosphoinositide 3-kinase (PI3K) pathway components and cell cycle factors in patients with prolonged survival after therapy. Gene expression analysis revealed up-regulation of PI3K-and cell cycle-related pathways in patients with shorter PFS. Conclusions: The OS and PFS of bevacizumab ± erlotinib-treated patients with renal cell carcinoma were associated with changes in expression of protein and gene expression markers related to PI3K pathway and cell cycle signaling.
Original language | English (US) |
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Pages (from-to) | 1599-1606 |
Number of pages | 8 |
Journal | Annals of Oncology |
Volume | 21 |
Issue number | 8 |
DOIs | |
State | Published - Jan 20 2010 |
Externally published | Yes |
Keywords
- Angiogenesis
- Bevacizumab
- Biomarker profiling
- Gene expression arrays
- Protein arrays
- Renal cell carcinoma
ASJC Scopus subject areas
- Hematology
- Oncology