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- Title
Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma.
- Authors
Zhang, Yong; Chen, Zhan; Chen, Jian‐Gang; Chen, Xin‐Feng; Gu, Dong‐Hua; Liu, Zhen‐Min; Gao, Ya‐Dong; Zheng, Bing
- Abstract
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.
- Subjects
RENAL cell carcinoma; SURVIVAL rate; CERULOPLASMIN; RENAL cancer; CELLULAR signal transduction; CELL adhesion
- Publication
FEBS Open Bio, 2021, Vol 11, Issue 11, p2988
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.13283