Abstract
Rho GDP dissociation inhibitor-β (ARHGDIB) is an important mediator of cell signaling. The expression of ARHGDIB is associated with tumor growth and metastasis in a variety of non-genitourinary cancers; however, the role of ARHGDIB in renal cell carcinoma (RCC) has not yet been evaluated. In the present study, tissue samples from 105 patients undergoing surgery for RCC were obtained. The expression levels of ARHGDIB mRNA in normal kidney tissues and in corresponding cancer tissues were analyzed by reverse transcription-quantitative polymerase chain reaction. Differences in relative mRNA expression levels were assessed using paired two-sample t-tests. Expression levels were analyzed with respect to various clinical parameters, and associations were tested using a bivariate logistic regression model. Relative mRNA expression levels in healthy renal tissues compared with cancerous tissues from the same kidney were assessed using paired t-tests. Expression data were compared with respect to survival data by the Kaplan-Meier method/Cox regression analysis. The results revealed that the relative mRNA expression level of ARHGDIB was significantly higher in the lysates of RCC tumor tissues (P<0.001) when compared with healthy renal tissues in a paired analysis of 74 samples; this finding was consistent with the analysis of ARHGDIB mRNA expression levels in all RCC samples, as well as in the subset of clear cell RCC (ccRCC) samples. The relative mRNA expression level of ARHGDIB was also increased in ccRCC tissues compared with papillary RCC tissues (P<0.001). On univariate Cox regression analysis, recurrence-free survival (RFS) was significantly associated with metastasis, locally advanced disease and tumor grade (P=0.018, P=0.002 and P<0.001, respectively). Furthermore, in the subgroup of patients with ccRCC, increased ARHGDIB mRNA expression was significantly associated with a longer RFS time (P=0.001). In summary, the results indicate that ARHGDIB mRNA is highly expressed in RCC tissues in general and is positively associated with RFS in ccRCC. As ARHGDIB has a known effect on angiogenesis and immune modulation, the present study suggests that the functional analysis of ARHGDIB should be performed in the future.
Highlights
Renal cell carcinoma (RCC) comprises 2‐3% of malignant tumors in the Western world [1]
The mRNA expression levels of ARHGDIB were more pronounced in clear cell RCC (ccRCC) tissues when compared with tissues from papillary RCC (papRCC) [P
The majority of members of the Ras family of GTPases act as molecular regulators, switching between an active GTP‐bound state with protein localization at the cellular membrane, and the cytosolic inactive protein bound to GDP [21]
Summary
Renal cell carcinoma (RCC) comprises 2‐3% of malignant tumors in the Western world [1]. It is an increasingly diagnosed malignancy, with an increased number of cases demonstrating a shift towards presenting with smaller renal masses, most likely due to the increasing use of computed tomography and ultrasonography [2]. A variety of genetic models have been proposed to account for the development of RCC, taking into account certain risk factors, such as cigarette smoking, hypertension and obesity [4]. Familial and sporadic forms of RCC can be associated with certain genetic alterations, the most common of which is the von Hippel‐Lindau tumor suppressor gene mutation [5,6]
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