Journal
CANCERS
Volume 12, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/cancers12020300
Keywords
everolimus; EVI1; genetic association; mTOR; clear cell renal cell carcinoma
Categories
Funding
- Generalitat de Catalunya [SGR 2017-449]
- Spanish Ministry of Health ISCIII [PI15/00854, PI18/01029]
- Telemaraton 2014 Todos Somos Raros, Todos Somos Unicos grant [P35]
- CERCA Programme of the Generalitat de Catalunya
- European Regional Development Fund (ERDF/FEDER, A way to make Europe)
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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-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.
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