Notch Signaling Pathway in Cancer—Review with Bioinformatic Analysis

SIMPLE SUMMARY: The Notch signaling pathway, which controls multiple cell differentiation processes during the embryonic stage and adult life, is associated with carcinogenesis and disease progression. The aim of the present study was to highlight cancer heterogeneity with respect to the Notch pathway. Our analysis concerns the effects of the Notch signaling at different levels, including core components and downstream target genes. We also demonstrate overall and disease-free survival results, pointing out the characteristics of particular Notch components. Depending on tissue context, Notch members can be either oncogenic or suppressive. We observed different expression profile core components and target genes that could be associated with distinct survival of patients. Advances in our understanding of the Notch signaling in cancer are very promising for the development of new treatment strategies for the benefit of patients. ABSTRACT: 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.