Abstract
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 IC50 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.
Highlights
The Notch signaling pathway plays an important role in cancer biology and is the focus of research on targeted therapy for cancer
We investigated the role of the Notch signaling pathway in clear cell renal cell carcinoma (ccRCC) and related therapeutic targets through bioinformatic analysis and established a Notchrelated prognosis model of ccRCC by using a LASSO estimate for linear regression to screen related genes, thereby providing a relatively meaningful strategy for the treatment of ccRCC
The results show that the expressions of 36 Notch pathway genes is abnormal in 72 normal kidney tissues and 539 kidney renal clear cell carcinoma (KIRC) samples obtained from The Cancer Genome Atlas (TCGA) (Figure 7(a))
Summary
The Notch signaling pathway plays an important role in cancer biology and is the focus of research on targeted therapy for cancer. The Notch signaling pathway is mainly composed of four parts, i.e., receptors, ligands, CSLDNA-binding protein, and downstream genes. The Notch signaling pathway is different from other important pathways, such as Wnt and TGF-β, and comprises receptors and ligands that mediate the activation of two cells after contact [2]. The Notch receptor is hydrolyzed by ADAM-γ-secrete to produce NICD, which binds to CSLDNA-binding proteins and activates downstream target genes [5]. The Notch signaling pathway has been shown to play an important role in homeostasis during cell development and the development and progression of diseases, especially those of cancer, with varying roles in various cancer tissues. We considered whether targeting the Notch signaling pathway could provide more possibilities for the treatment of ccRCC
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