Gene expression pattern of the epidermal growth factor receptor family and LRIG1 in renal cell carcinoma

Abstract

Background: Previous studies have revealed altered expression of epidermal growth factor receptor (EGFR)-family members and their endogenous inhibitor leucine-rich and immunoglobulin-like domains 1 (LRIG1) in renal cell carcinoma (RCC). In this study, we analyzed the gene expression levels of EGFR-family members and LRIG1, and their possible associations with clinical parameters in various types of RCC.

Methods: Gene expression levels of EGFR-family members and LRIG1 were analyzed in 104 RCC samples, including 81 clear cell RCC (ccRCC), 15 papillary RCC (pRCC), and 7 chromophobe RCC (chRCC) by quantitative real-time RT-PCR. Associations between gene expression levels and clinical data, including tumor grade, stage, and patient survival were statistically assessed.

Results: Compared to kidney cortex, EGFR was up-regulated in ccRCC and pRCC, LRIG1 and ERBB2 were down-regulated in ccRCC, and ERBB4 was strongly down-regulated in all RCC types. ERBB3 expression did not differ between RCC types or between RCC and the kidney cortex. The expression of the analyzed genes did not correlate with patient outcome.

Conclusions: This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed RCC types, whereas down-regulation of ERBB2 and LRIG1 was only present in ccRCC. These observations illustrate the need to evaluate the different RCC types individually when analyzing molecules of interest and potential biological markers.

Figure 1

Boxplots of the relative mRNA expression of theEGFR-family members andLRIG1in both the kidney cortex and the RCC types. Relative mRNA expression of EGFR, ERBB2, ERRB3, ERRB4, and LRIG1 was quantified in kidney cortex (n = 27), ccRCC (n = 81), pRCC (n = 15), and chRCC (n = 7). (A) EGFR mRNA expression was elevated in ccRCC and pRCC compared to kidney cortex. (Increased expression in chRCC was not significant, but expression levels were similar to other RCC groups.) (B) ERBB2 mRNA expression was significantly lower in ccRCC compared to kidney cortex. In pRCC and chRCC, expression did not significantly differ from kidney cortex. (C) ERBB3 mRNA expression was not significantly different between any of the RCC types compared to the kidney cortex. (D) ERBB4 mRNA expression was significantly reduced in all RCC types compared to kidney cortex. (E) LRIG1 mRNA expression was significantly lower in ccRCC compared to kidney cortex. In pRCC and chRCC, LRIG1 expression did not significantly differ from kidney cortex. Outlier values are marked °. Significant differences compared to expression in the kidney cortex are labeled (*) for P < 0.05 and (**) for P < 0.01.