Identification of Prognostic Stemness-related Genes in Kidney Renal Papillary Cell Carcinoma

Abstract Background Kidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells (CSC) and stemness-related genes (SRGs) are constantly revealed to play important roles in carcinogenesis and metastasis of various tumors. In the present study, we aim to investigate the underlying mechanisms of stemness-related genes (SRGs) in carcinogenesis and metastasis of KIRP. Methods RNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, which was used to identify differentially expressed genes (DEGs). The univariate Cox analysis was used to identify the significant stemness-related genes (SRGs) with prognostic value, based on which we calculated the risk score and established a prognostic model by multivariate Cox regression in KIRP patients. In addition, the regulatory network of SRGs, upstream transcription factors (TFs), and downstream signaling pathways was constructed by the Pearson correlation analysis. Results In total, 1124 genes were characterized as DEGs between low- and high-stemness groups. Based on six prognostic SRGs, a prediction model was established with an AUC of 0.861. Furthermore, the transcription factor CBX2 was co-expressed with the stemness-related gene ASPH (R = 0.46, P < 0.001), and ASPH had a significant co-expression pattern with the Notch signaling pathway (R = 0.42, P < 0.001). Meanwhile, we also found that resveratrol might be a potential inhibitor for KIRP. Conclusions We suggested that CBX2 regulated ASPH through activation of Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.