Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis.
Objectives: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters.Material and methods: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The...
| Authors: | , , , , , , |
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| Format: | article |
| Publication Date: | 2017 |
| Country: | España |
| Institution: | Universidad de Castilla-La Mancha |
| Repository: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/34247 |
| Online Access: | https://hdl.handle.net/10578/34247 |
| Access Level: | Open access |
| Keyword: | Biomarkers Clear cell renal cell carcinoma Signaling pathway VHL |
| Summary: | Objectives: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters.Material and methods: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables. A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable.Results: The study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014).Conclusions: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages. |
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