Palomero Luis, Bodnar Lubomir, Mateo Francesca, Herranz-Ors Carmen, Espín Roderic, García-Varelo Mar, Jesiotr Marzena, Ruiz de Garibay Gorka, Casanovas Oriol, López José I, Pujana Miquel Angel
ProCURE, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona 08908, Catalonia, Spain.
Department of Oncology and Immunooncology, Hospital Ministry of the Interior and Administration with Warmia and Mazury Oncology Center, Olsztyn 10-719, Poland.
Cancers (Basel). 2020 Jan 28;12(2):300. doi: 10.3390/cancers12020300.
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 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 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC.
转录因子EVI1通过促进侵袭性癌症特征在多种肿瘤中发挥致癌作用。EVI1有助于表观遗传调控和转录控制，在某些情况下，其过表达与PI3K-AKT-mTOR信号增强有关。这些观察结果提示，EVI1可能影响透明细胞肾细胞癌（ccRCC）的预后以及基于依维莫司的治疗效果。在此，ccRCC的基因表达和蛋白质免疫组化研究表明，EVI1过表达与疾病进展及较差的预后相关，尤其是在癌症基因组图谱定义的CC-e.3亚型中。RCC细胞系中致癌性EVI1亚型的过表达赋予了对依维莫司的显著抗性。rs1344555基因变异与接受依维莫司治疗的转移性ccRCC患者较差的生存率和更高的疾病进展相关。这项研究使我们提出，评估EVI1蛋白或基因表达以及基因变异可能有助于改善对ccRCC预后的估计以及基于依维莫司治疗的获益情况。
