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   <dc:title>Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis</dc:title>
   <dc:creator>Serrano-Oviedo, Leticia</dc:creator>
   <dc:creator>Giménez-Bachs, José Miguel</dc:creator>
   <dc:creator>Nam-Cha, Syong Hyun</dc:creator>
   <dc:creator>Cimas, Francisco J.</dc:creator>
   <dc:creator>García-Cano, Jesús</dc:creator>
   <dc:creator>Sánchez-Prieto, Ricardo</dc:creator>
   <dc:creator>Salinas-Sánchez, Antonio S.</dc:creator>
   <dc:subject>Proteïnes</dc:subject>
   <dc:subject>Biologia molecular</dc:subject>
   <dc:subject>Marcadors tumorals</dc:subject>
   <dc:subject>Càncer de ronyó</dc:subject>
   <dc:subject>Metàstasi</dc:subject>
   <dc:subject>Proteins</dc:subject>
   <dc:subject>Molecular biology</dc:subject>
   <dc:subject>Tumor markers</dc:subject>
   <dc:subject>Renal cancer</dc:subject>
   <dc:subject>Metastasis</dc:subject>
   <dc:description>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&lt;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&lt;0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P&lt;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.</dc:description>
   <dc:date>2017-05-12T08:33:58Z</dc:date>
   <dc:date>2017-11-08T23:01:27Z</dc:date>
   <dc:date>2016-11-08</dc:date>
   <dc:date>2017-05-12T08:33:58Z</dc:date>
   <dc:type>info:eu-repo/semantics/article</dc:type>
   <dc:type>info:eu-repo/semantics/acceptedVersion</dc:type>
   <dc:identifier>1078-1439</dc:identifier>
   <dc:identifier>https://hdl.handle.net/2445/110906</dc:identifier>
   <dc:identifier>670347</dc:identifier>
   <dc:language>eng</dc:language>
   <dc:relation>Versió postprint del document publicat a: https://doi.org/10.1016/j.urolonc.2016.10.010</dc:relation>
   <dc:relation>Urologic Oncology-Seminars and Original Investigations, 2017, vol. 35, num. 3, p. 114.e15-114.e22</dc:relation>
   <dc:relation>https://doi.org/10.1016/j.urolonc.2016.10.010</dc:relation>
   <dc:rights>cc-by-nc-nd (c) Elsevier Inc. , 2016</dc:rights>
   <dc:rights>http://creativecommons.org/licenses/by-nc-nd/3.0/es</dc:rights>
   <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
   <dc:format>8 p.</dc:format>
   <dc:format>application/pdf</dc:format>
   <dc:publisher>Elsevier Inc.</dc:publisher>
   <dc:source>Articles publicats en revistes (Ciències Fisiològiques)</dc:source>
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