Rho GDP dissociation inhibitor beta ARHGDIB in renal cell cancer.

Abstract

474 Background: Rho GDP dissociation inhibitor 2 (ARHGDIB) is an important mediator of cellular signaling. The expression of ARHGDIB correlates with tumor growth and metastasis in a variety of non genitourinary cancers, however the role of ARHGDIB in renal cell cancer (RCC) has not yet been evaluated. Methods: Tissue samples from 106 patients undergoing surgery for RCC were obtained. The expression of ARHGDIB mRNA in normal kidney tissue and in corresponding cancer tissue was analyzed by means of quantitative real time PCR. Differences in mRNA expression levels were assessed using paired two-sample tests. Associations of relative mRNA expression levels and clinicopathological parameters were statistically analyzed using an univariate logistic regression model. Relative mRNA expression levels in healthy renal tissue compared to cancerous tissue from the same kidney was assessed using a paired t-test. Results: When comparing 74 tissues from kidney tumors with adjacent histologically normal appearing paired tissues, mRNA expression of ARHGDIB was significantly higher in the tumor tissue (p < 0.001). Paired analysis did not only show significantly higher mRNA expression levels for ARHGDIB over all RCC but also for the subgroup with clear cell RCC (ccRCC). The mRNA expression of ARHGDIB was also more pronounced in ccRCC when compared with papillary RCC (p < 0.001). When looking at clinicopathological parameters in univariate logistic regression analysis ccRCC was significantly associated with nodal involvement (p = 0.03) and also with tumor grade (p = 0.05). For all RCC there was no association with clinicopathological parameters. A bivariate Cox regression model, adjusted for metastatic status (p = 0.001), tumor diameter (p = 0.043), state of advanced disease (p = 0.030) and lymph node metastasis (p = 0.006) identified ARHGDIB mRNA expression as a candidate positive prognosticator for RFS. Conclusions: Increased ARHGDIB mRNA expression is significantly associated with RCC tissues. Higher relative expression observed within tumor tissues represents a candidate prognosticator for better RFS of patients.