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Functional transcriptomic annotation and protein–protein interaction analysis identify EZH 2 and UBE 2C as key upregulated proteins in ovarian cancer

2018; Wiley; Volume: 7; Issue: 5 Linguagem: Inglês

10.1002/cam4.1406

2045-7634

Sandra Martínez‐Canales, Miguel López de Rodas, Miriam Nuncia‐Cantarero, Raquel Páez, Eitan Amir, Balázs Győrffy, Atanasio Pandiella, Eva María Galán‐Moya, Alberto Ocaña,

Histone Deacetylase Inhibitors Research

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 , CDK 1, BIRC 5, or CHEK 1 among others. Of note, the histone‐lysine N‐methyltransferase ( EZH 2 ) and the ubiquitin‐conjugating enzyme E2C ( UBE 2C ) genes were found to be upregulated and amplified in 10% and 6% of tumors, respectively. Of note, EZH 2 and UBE 2C 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 EZH 2 and UBE 2C .