Anusewicz Dorota, Orzechowska Magdalena, Bednarek Andrzej K
Department of Molecular Carcinogenesis, Medical University of Lodz, 90-752 Lodz, Poland.
Cancers (Basel). 2021 Feb 12;13(4):768. doi: 10.3390/cancers13040768.
Notch signaling is an evolutionarily conserved pathway regulating normal embryonic development and homeostasis in a wide variety of tissues. It is also critically involved in carcinogenesis, as well as cancer progression. Activation of the Notch pathway members can be either oncogenic or suppressive, depending on tissue context. The present study is a comprehensive overview, extended with a bioinformatics analysis of TCGA cohorts, including breast, bladder, cervical, colon, kidney, lung, ovary, prostate and rectum carcinomas. We performed global expression profiling of the Notch pathway core components and downstream targets. For this purpose, we implemented the Uniform Manifold Approximation and Projection algorithm to reduce the dimensions. Furthermore, we determined the optimal cutpoint using Evaluate Cutpoint software to established disease-free and overall survival with respect to particular Notch members. Our results demonstrated separation between tumors and their corresponding normal tissue, as well as between tumors in general. The differentiation of the Notch pathway, at its various stages, in terms of expression and survival resulted in distinct profiles of biological processes such as proliferation, adhesion, apoptosis and epithelial to mesenchymal transition. In conclusion, whether oncogenic or suppressive, Notch signaling is proven to be associated with various types of malignancies, and thus may be of interest as a potential therapeutic target.
Notch信号通路是一条在进化上保守的信号通路，可调节多种组织中的正常胚胎发育和内环境稳态。它在致癌作用以及癌症进展中也起着关键作用。Notch信号通路成员的激活可能具有致癌性或抑制性，这取决于组织背景。本研究是一项全面综述，并扩展了对TCGA队列（包括乳腺癌、膀胱癌、宫颈癌、结肠癌、肾癌、肺癌、卵巢癌、前列腺癌和直肠癌）的生物信息学分析。我们对Notch信号通路的核心成分和下游靶点进行了全基因组表达谱分析。为此，我们采用了均匀流形近似和投影算法来降维。此外，我们使用“评估切点”软件确定了最佳切点，以建立特定Notch成员的无病生存期和总生存期。我们的结果表明肿瘤与其相应的正常组织之间以及一般肿瘤之间存在区分。Notch信号通路在其不同阶段在表达和生存方面的差异导致了增殖、黏附、凋亡和上皮-间质转化等生物过程的不同特征。总之，无论具有致癌性还是抑制性，Notch信号通路都被证明与多种类型的恶性肿瘤相关，因此作为潜在的治疗靶点可能具有研究价值。
