Gene and protein expression markers of response to combined antiangiogenic and epidermal growth factor targeted therapy in renal cell carcinoma.
Ann Oncol, 2010/8;21(8):1599-1606.
Tsavachidou-Fenner D[1], Tannir N[2], Tamboli P[3], Liu W[4], Petillo D[5], Teh B[5], Mills GB[1], Jonasch E[6]
Affiliations
PMID: 20089566DOI: 10.1093/annonc/mdp600
Impact factor: 51.769
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.
MeSH terms
Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Cycle; Epidermal Growth Factor; Gene Expression Profiling; Humans; Kidney Neoplasms; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Survival Analysis; Vascular Endothelial Growth Factor A
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