Abstract B29: Role of inflammatory-related gene expression in clear cell renal cell carcinoma

Abstract

Abstract Renal cell carcinoma (RCC) is the 10th most common cancer in United States with clear-cell renal carcinoma (ccRCC) being the most common. Many genes and signaling pathways have been implicated in ccRCC development, including the inflammation pathway. However, less is known about how gene expression variation within this pathway influences ccRCC development and clinical outcomes. Gene expression in tumor and adjacent normal tissues from 93 patients with ccRCC was detected using a genome-wide expression array and a panel of 661 inflammation-related genes was then analyzed. Differential expression patterns between tumor and adjacent normal tissue were observed. Association between expression and recurrence or survival was evaluated with those genes showing significant association further tested in a validation set of 258 ccRCC tumor samples. A total of 151 genes with at least a 2-fold change in gene expression between adjacent normal and tumor were identified, with a majority of the genes being upregulated in the tumors. Eleven inflammation-related genes (BLNK, APP, IL8, CARD9, SOD2, IL10RA, GADD45G, ADORA3, CXCL1, CIITA, and NCF2) were found to be significantly associated with recurrence and/or overall survival in 93 ccRCC tumors and selected for further validation. Expression of CIITA and NCF2 was significantly associated with overall survival in the replication dataset with high expression levels associated with significant 2.65-fold (95% CI=1.28-5.49, P=0.0088) and a 2.26-fold (95% CI=1.12-4.58, P=0.023) increased risk of dying, respectively. Our results suggest expression of CIITA and NCF2 genes may be significant prognostic biomarkers for risk of dying in patients with ccRCC. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B29.