Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment
| العنوان: | Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear‑cell renal cell carcinoma treated with sunitinib as first‑line treatment |
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| المؤلفون: | Agnieszka Rybarczyk, Aleksandra Ludziejewska, Piotr M. Wierzbicki, Jakub Klacz, Zbigniew Kmieć, Marcin Stanisławowski, Agata Wronska, Marcin Matuszewski, Anna Kotulak‑Chrzaszcz |
| المصدر: | International Journal of Oncology |
| بيانات النشر: | Spandidos Publications, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Vascular Endothelial Growth Factor A, p53, 0301 basic medicine, Cancer Research, clear cell renal cell carcinoma, urologic and male genital diseases, Tyrosine-kinase inhibitor, Metastasis, 0302 clinical medicine, sunitinib resistance, Basic Helix-Loop-Helix Transcription Factors, Sunitinib, Aged, 80 and over, Articles, Middle Aged, Prognosis, Kidney Neoplasms, female genital diseases and pregnancy complications, Gene Expression Regulation, Neoplastic, Survival Rate, Vascular endothelial growth factor A, Oncology, Von Hippel-Lindau Tumor Suppressor Protein, 030220 oncology & carcinogenesis, western blot analysis, Female, hypoxia-inducible factor 1 subunit α, metastatic disease, medicine.drug, Adult, medicine.drug_class, Biology, 03 medical and health sciences, Biomarkers, Tumor, medicine, Humans, reverse transcription-quantitative polymerase chain reaction, Carcinoma, Renal Cell, Protein Kinase Inhibitors, Survival rate, Aged, Cancer, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Von Hippel-Lindau tumor suppressor, Clear cell renal cell carcinoma, 030104 developmental biology, HIF1A, gene expression, Cancer research, Tumor Suppressor Protein p53, hypoxia-inducible factor 2α, Follow-Up Studies |
| الوصف: | 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 Hippel-Lindau tumor suppressor (VHL)-hypoxia-inducible factor 1 subunit α (HIF1A)/hypoxia-inducible 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 first-line therapy following nephrec-tomy. A total of 36 ccRCC patients were enrolled, 11 of whom were administered sunitinib post-operatively. Tumor and control samples were collected, and mRNA and protein levels were assessed by reverse transcription-quantitative 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 progression-free 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 |
| تدمد: | 1791-2423 1019-6439 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9ee87048b0565a401aae693181e953aTest https://doi.org/10.3892/ijo.2019.4830Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e9ee87048b0565a401aae693181e953a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17912423 10196439 |
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