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The Notch family of genes encodes a group of highly conserved cell surface membrane receptors, which are involved in one of the key pathways that determine cell growth, differentiation, and apoptosis in embryonic tissues. Furthermore, abnormal expression of Notch genes is closely related to the occurrence and development of several cancers. To date, no specific treatment of RCC has been reported to relate to the Notch pathway. Therefore, we detected Notch pathway genes in series of tumors, as well as potential compounds targeting the Notch pathway, with a focus on the mechanism of Notch pathway action in kidney renal clear cell carcinoma (KIRC). Samples from KIRC patients were divided into three clusters based on the mRNA expression of Notch pathway genes. In addition, we investigated the potential targets of the Notch pathway, predicted the IC 50 of several classical targeted therapies, and analyzed their correlation with the Notch pathway. Finally, LASSO regression analysis was performed to build a model to predict survival in KIRC patients. These results suggest that therapies targeting the Notch pathway could be more efficiently studied based on the Notch score and that we can predict the prognosis of patients with KIRC based on the expression of Notch pathway genes. Most importantly, these results may provide a solid theoretical basis for future research on therapeutic targets for patients with KIRC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ziyao Li et al.)