Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma

FEBS Open Bio

Ya‐Dong Gao¹  Xin‐Feng Chen²  Zhen‐Min Liu²  Dong‐Hua Gu²  Bing Zheng²  Yong Zhang²  Zhan Chen²  Jian‐Gang Chen² 

[1] Department of Medical Research Center The Second Affiliated Hospital of Nantong University China;Department of Urology The Second Affiliated Hospital of Nantong University China;

关键词: bioinformatics analysis;    biomarker;    diagnosis;    differentially expressed genes;    prognosis;    renal cell carcinoma;   

DOI  :  10.1002/2211-5463.13283

来源: DOAJ

【 摘 要 】

Clear‐cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy. The pathogenesis of the disease is currently poorly understood, and the prognosis is poor. Therefore, in this study, we focused on exploring and identifying genes and signal transduction pathways that are closely related to ccRCC. Differentially expressed genes (DEGs) were analyzed using the renal cell oncogene expression profiles GSE100666 and GSE68417. DAVID evaluation of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was used. We constructed a protein–protein interaction (PPI) network of DEGS using Cytoscape software and analyzed the submodules with the CytoHubba plugin. Finally, we performed western blot, immunohistochemistry, and PCR validation by collecting tissues, and also utilized cells for in vitro functional analysis of ceruloplasmin (CP). In total, 202 DEGs (52 upregulated and 150 downregulated genes) were identified. Upregulated DEGs are significantly rich in angiogenesis, cell adhesion, and response to hypoxia, whereas downregulated DEGs are involved in intracellular pH regulation, excretion, coagulation, and chloride transmembrane transport. We selected the interactions of the top 20 hub genes provided by the PPI network, all of which are involved in important physiological pathways in vivo, such as complement and coagulation cascades. Tissue protein assays demonstrated that renal cancer highly expressed CP, while in vitro experiments showed that CP could promote the invasion of renal cancer cells. Our study suggests that ALB, C3, LOX, HRG, CXCR4, GPC3, SLC12A3, CP, and CASR may be involved in the development of ccRCC, and is expected to provide theoretical support for future studies on the diagnosis and targeted therapy of ccRCC.

【 授权许可】

Unknown