Interferon-alpha resistance associated genes in renal cell carcinoma identified by expression profiling.

Overview

PURPOSE: We identified differentially expressed genes associated with response to pegylated interferon-alpha treatment in patients with renal cell carcinoma. MATERIALS AND METHODS: We performed expression profiling on renal cell carcinoma specimens isolated from 23 patients with metastatic disease who were subsequently treated with interferon. Significance Analysis for Microarrays software was used to identify genes that were differentially expressed between patients with partial response compared to those with disease progression. RESULTS: A candidate gene approach looking at VHL and known target genes did not identify any genes whose expression correlated with patient response. A global analysis of approximately 54,000 probe sets identified 4 genes that had expression correlated with response. Reverse transcriptase-polymerase chain reaction analysis of 2 of these genes confirmed that they were more highly expressed in tumors from patients who responded to interferon-alpha. Interestingly, both of these genes mapped to 4q31-32, a region that has been implicated as the site of a potential tumor suppressor gene in renal cell carcinoma. CONCLUSIONS: We have identified 4 genes (3 uncharacterized and 1 known) that may prove useful in predicting response to interferon-alpha treatment in patients with renal cell carcinoma.