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Cancer Med. 2018 May;7(5):1896-1907. doi: 10.1002/cam4.1406. Epub 2018 Mar 25.

Functional transcriptomic annotation and protein-protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer.

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Translational Research Unit and Translational Oncology Laboratory, Albacete University Hospital and Centro Regional de Investigaciones Biomedicas, Castilla-La Mancha University (CRIB-UCLM), Albacete, Spain.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Semmelweis University 2nd Department of Pediatrics, Budapest, Hungary.
Cancer Research Center and CIBERONC, CSIC, Salamanca, Spain.


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.


Clinical outcome; EZH2; Ovarian cancer; UBE2C; druggable proteins; protein-protein interaction

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