Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clearcell renal cell carcinoma treated with sunitinib as firstline treatment.
Int J Oncol
; 55(2): 371-390, 2019 Aug.
Article
en En
| MEDLINE
| ID: mdl-31268155
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell cancer, characterized by the highest mortality rate among other RCC subtypes due to the occurrence of metastasis and drug resistance following surgery. The Von HippelLindau tumor suppressor (VHL)hypoxiainducible factor 1 subunit α (HIF1A)/hypoxiainducible factor 2α (HIF2A)vascular endothelial growth factor A (VEGFA) protein axis is involved in the development and progression of ccRCC, whereas sunitinib, a tyrosine kinase inhibitor, blocks the binding of VEGFA to its receptor. The aim of the present study was to examine the possible association of the gene expression of VHL, HIF1A, HIF2A, VEGFA and tumor protein P53 (P53) in cancer tissue with the outcome of ccRCC patients who were treated with sunitinib as firstline therapy following nephrectomy. A total of 36 ccRCC patients were enrolled, 11 of whom were administered sunitinib postoperatively. Tumor and control samples were collected, and mRNA and protein levels were assessed by reverse transcriptionquantitative polymerase chain reaction and western blot analysis, respectively. High mRNA and protein expression levels of HIF2A and VEGFA were found to be associated with shorter overall survival (OS) and progressionfree survival (PFS) rates, as well as with unfavorable risk factors of cancer recurrence and mortality. Resistance to sunitinib was also observed; the OS and PFS rates were shorter (median OS and PFS 12 and 6 months, respectively, vs. undetermined). Sunitinib resistance was associated with high HIF2A and VEGFA protein levels (b=0.57 and b=0.69 for OS and PFS, respectively; P<0.001). Taken together, the findings of this study suggest that the protein levels of HIF2A and VEGFA in tumor tissue may serve as independent prognostic factors in ccRCC. ccRCC patients with increased intratumoral HIF2A and VEGFA protein levels, and unaltered VHL protein levels, are not likely to benefit from sunitinib treatment following nephrectomy; however, this hypothesis requires verification by largescale replication studies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
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Proteína p53 Supresora de Tumor
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Factor A de Crecimiento Endotelial Vascular
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Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Sunitinib
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Polonia