Author:
Liu Yifan,Yao Yuntao,Zhang Yu,Xu Chengdang,Yang Tianyue,Qu Mingyu,Lu Bingnan,Song Xu,Pan Xiuwu,Zhou Wang,Cui Xingang
Abstract
Abstract
Background
Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP.
Methods
RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors.
Results
In total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP.
Conclusions
We suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.
Funder
National Natural Science Foundation of China
Shanghai Rising-Star Program
Shanghai Municipal Health and Family Planning Commission
Leading health talents of Shanghai Municipal Health Commission
Natural Science Foundation of Shanghai Municipality
Hospital Funded Clinical Research, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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