Wang Lulu, Liu Xiaowei
Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Front Genet. 2022 May 12;13:814725. doi: 10.3389/fgene.2022.814725. eCollection 2022.
The DREAM complex is an evolutionarily conserved cell cycle regulating multi-protein complex. In addition to playing an essential function in the cell cycle, it also plays a vital role in various survival activities. Accumulating evidence suggests that the DREAM complex plays a crucial role in oncogenesis. However, the regulatory mechanism of the DREAM complex in cancer remains unclear. This study used multi-omics data from Cancer Genome Atlas and Cancer Cell Line Encyclopedia to comprehensively identify the DREAM complex in tumor samples from 33 cancer types. In the genomic landscape, we identified the missense mutation as the dominant alteration events. Expression analysis showed that the expression of methylation-mediated the DREAM complex was downregulated. In addition, we found that the expression of the DREAM complex can be performed to predict the survival of various cancer patients. Pathway activation analysis showed that the DREAM complex is related to apoptosis inhibition, cell cycle, DNA damage response, RAS/MAPK, and RTK signaling pathway activation. Importantly, through a comprehensive analysis of drug sensitivity genomics in cancer databases, we identified a number of potential drugs that may target the DREAM complex. In summary, this study revealed the genomic changes and clinical features of the DREAM complex in 33 cancers, which may also provide new insights for cancer treatment and may offer alternative options for the treatment of clinically refractory cancers.
DREAM复合体是一种进化上保守的细胞周期调节多蛋白复合体。除了在细胞周期中发挥重要功能外,它在各种生存活动中也起着至关重要的作用。越来越多的证据表明,DREAM复合体在肿瘤发生中起关键作用。然而,DREAM复合体在癌症中的调控机制仍不清楚。本研究使用来自癌症基因组图谱和癌症细胞系百科全书的多组学数据,全面鉴定了33种癌症类型肿瘤样本中的DREAM复合体。在基因组格局中,我们将错义突变确定为主要的改变事件。表达分析表明,甲基化介导的DREAM复合体表达下调。此外,我们发现DREAM复合体的表达可用于预测各种癌症患者的生存情况。通路激活分析表明,DREAM复合体与凋亡抑制、细胞周期、DNA损伤反应、RAS/MAPK和RTK信号通路激活有关。重要的是,通过对癌症数据库中药物敏感性基因组学的综合分析,我们鉴定出了一些可能靶向DREAM复合体的潜在药物。总之,本研究揭示了33种癌症中DREAM复合体的基因组变化和临床特征,这也可能为癌症治疗提供新的见解,并可能为临床难治性癌症的治疗提供替代选择。