Functional transcriptomic annotation and protein–protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer. (25th March 2018)

• Record Type: Journal Article
• Authors: Martínez‐Canales, Sandra; López de Rodas, Miguel; Nuncia‐Cantarero, Miriam; Páez, Raquel; Amir, Eitan; Győrffy, Balázs; Pandiella, Atanasio; Galán‐Moya, Eva María; Ocaña, Alberto
• Is Part Of: Cancer medicine. Volume 7:Number 5(2018:May)
• Page Start: 1896
• Page End: 1907
• Publication Date: 2018-03-25
• Subjects: Clinical outcome -- druggable proteins -- EZH2 -- Ovarian cancer -- protein–protein interaction -- UBE2C; 616.994005
• DOI: 10.1002/cam4.1406
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Although early stage ovarian cancer is in most cases a curable disease, some patients relapse even with appropriate adjuvant treatment. Therefore, the identification of patient and tumor characteristics to better stratify risk and guide rational drug development is desirable. Using transcriptomic functional annotation followed by protein–protein interacting (PPI) network analyses, we identified functions that were upregulated and associated with detrimental outcome in patients with early stage ovarian cancer. Some of the identified functions included cell cycle, cell division, signal transduction/protein modification, cellular response to extracellular stimuli or transcription regulation, among others. Genes within these functions included AURKA, AURKB, CDK1, BIRC5, or CHEK1 among others. Of note, the histone‐lysine N‐methyltransferase ( EZH2 ) and the ubiquitin‐conjugating enzyme E2C ( UBE2C ) genes were found to be upregulated and amplified in 10% and 6% of tumors, respectively. Of note, EZH2 and UBE2C were identified as principal interacting proteins of druggable networks. In conclusion, we describe a set of genes overexpressed in ovarian cancer with potential for therapeutic intervention including EZH2 and UBE2C . Abstract : In this study, we identified deregulated functions in early stage ovarian cancer that are associated with worse outcome and, therefore, identify patients at higher risk. Moreover, EZH2 and UBE2C were identified as potential druggable targets in ovarian cancer.