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

机译:功能性转录组注释和蛋白质-蛋白质相互作用分析确定EZH2和UBE2C是卵巢癌中的关键上调蛋白质

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摘要

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.
机译:尽管早期卵巢癌在大多数情况下是可以治愈的疾病,但即使采用适当的辅助治疗,仍有一些患者复发。因此,鉴定患者和肿瘤特征以更好地分层风险并指导合理的药物开发是理想的。使用转录组功能注释,然后进行蛋白质-蛋白质相互作用(PPI)网络分析,我们确定了早期卵巢癌患者中被上调并与有害结果相关的功能。一些已确定的功能包括细胞周期,细胞分裂,信号转导/蛋白质修饰,细胞对细胞外刺激或转录调控的反应等。这些功能内的基因包括AURKA,AURKB,CDK1,BIRC5或CHEK1等。值得注意的是,组蛋白-赖氨酸N-甲基转移酶(EZH2)和泛素结合酶E2C(UBE2C)基因分别在10%和6%的肿瘤中被上调和扩增。值得注意的是,EZH2和UBE2C被确定为可药物网络的主要相互作用蛋白。总之,我们描述了一组在卵巢癌中过表达的基因,具有治疗干预的潜力,包括EZH2和UBE2C。

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