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Rho GDP dissociation inhibitor-β in renal cell carcinoma
Christoph-Alexander von Klot1, Natalia Dubrowinskaja1, Inga Peters1
1Department of Urology and Urological Oncology, Hannover University Medical School, D-30625 Hannover, Germany.
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.
Insights
Rho GDP dissociation inhibitor-β (ARHGDIB) is highly expressed in renal cell carcinoma (RCC) tissues. Increased ARHGDIB mRNA expression is linked to longer recurrence-free survival in clear cell RCC, suggesting a potential role in kidney cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Rho GDP dissociation inhibitor-β (ARHGDIB) is a key cell signaling mediator implicated in tumor growth and metastasis in various cancers.
- The specific role of ARHGDIB in renal cell carcinoma (RCC), a significant non-genitourinary cancer, remains largely uninvestigated.
- Understanding ARHGDIB's function in RCC is crucial for identifying potential therapeutic targets and prognostic markers.
Purpose of the Study:
- To evaluate the expression levels of ARHGDIB mRNA in renal cell carcinoma (RCC) tissues compared to normal kidney tissues.
- To investigate the association between ARHGDIB expression and clinical parameters, including patient survival.
- To explore the differential expression of ARHGDIB in various subtypes of RCC, such as clear cell RCC (ccRCC) and papillary RCC.
Main Methods:
- Quantitative analysis of ARHGDIB mRNA expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) on 105 RCC patient tissue samples.
- Statistical analysis including paired t-tests to compare cancerous and healthy tissues, and bivariate logistic regression to assess associations with clinical parameters.
- Kaplan-Meier method and Cox regression analysis were employed to correlate ARHGDIB expression with recurrence-free survival (RFS).
Main Results:
- ARHGDIB mRNA expression was significantly elevated in RCC tumor tissues compared to adjacent healthy renal tissues (P<0.001).
- Higher ARHGDIB mRNA levels were observed in clear cell RCC (ccRCC) tissues relative to papillary RCC tissues (P<0.001).
- In ccRCC patients, increased ARHGDIB mRNA expression was significantly associated with a longer recurrence-free survival (RFS) (P=0.001).
Conclusions:
- ARHGDIB is significantly overexpressed in renal cell carcinoma (RCC) tissues.
- ARHGDIB mRNA expression is positively associated with recurrence-free survival (RFS) in clear cell RCC (ccRCC) patients.
- Further functional studies on ARHGDIB are warranted due to its known roles in angiogenesis and immune modulation, suggesting its potential as a therapeutic target in RCC.
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