Interferon-alpha resistance associated genes in renal cell carcinoma identified by expression profiling.
OBJECTIVE
We identified differentially expressed genes associated with response to pegylated interferon-alpha treatment in patients with renal cell carcinoma.


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.
Korkola
James E
JE
Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kondagunta
G Varuni
GV
Reuter
Victor E
VE
Motzer
Robert J
RJ
Chaganti
R S K
RS
D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics*
D016898:Interferon-alpha