EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma
Autor: | Francesca Mateo, Marzena Jesiotr, Luis Palomero, Mar García-Varelo, Carmen Herranz-Ors, Lubomir Bodnar, José I. López, Roderic Espín, Oriol Casanovas, Miquel Angel Pujana, Gorka Ruiz de Garibay |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Gene isoform Cancer Research genetic association clear cell renal cell carcinoma lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Gene expression Transcriptional regulation Medicine Epigenetics Càncer Transcription factor PI3K/AKT/mTOR pathway Cancer Everolimus business.industry Immunosupressive agents lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease everolimus EVI1 Clear cell renal cell carcinoma 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research mTOR Immunosupressors business medicine.drug |
Zdroj: | Cancers Dipòsit Digital de la UB Universidad de Barcelona Volume 12 Issue 2 Cancers, Vol 12, Iss 2, p 300 (2020) |
ISSN: | 2072-6694 |
Popis: | The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistochemical studies of ccRCC show that EVI1 overexpression is associated with advanced disease features and with poorer outcome&mdash particularly in the CC-e.3 subtype defined by The Cancer Genome Atlas. Overexpression of an oncogenic EVI1 isoform in RCC cell lines confers substantial resistance to everolimus. The EVI1 rs1344555 genetic variant is associated with poorer survival and greater progression of metastatic ccRCC patients treated with everolimus. This study leads us to propose that evaluation of EVI1 protein or gene expression, and of EVI1 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC. |
Databáze: | OpenAIRE |
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