Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma
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...
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| Format: | Article |
| Language: | English |
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Wiley
2021-11-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13283 |
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| author | Yong Zhang Zhan Chen Jian‐Gang Chen Xin‐Feng Chen Dong‐Hua Gu Zhen‐Min Liu Ya‐Dong Gao Bing Zheng |
| author_facet | Yong Zhang Zhan Chen Jian‐Gang Chen Xin‐Feng Chen Dong‐Hua Gu Zhen‐Min Liu Ya‐Dong Gao Bing Zheng |
| author_sort | Yong Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T17:54:57Z |
| format | Article |
| id | doaj.art-b8e76db59bbc40b88764f66f029e3ab0 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-19T17:54:57Z |
| publishDate | 2021-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-b8e76db59bbc40b88764f66f029e3ab02022-12-21T20:11:50ZengWileyFEBS Open Bio2211-54632021-11-0111112988300410.1002/2211-5463.13283Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinomaYong Zhang0Zhan Chen1Jian‐Gang Chen2Xin‐Feng Chen3Dong‐Hua Gu4Zhen‐Min Liu5Ya‐Dong Gao6Bing Zheng7Department of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaDepartment of Medical Research Center The Second Affiliated Hospital of Nantong University ChinaDepartment of Urology The Second Affiliated Hospital of Nantong University ChinaClear‐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.https://doi.org/10.1002/2211-5463.13283bioinformatics analysisbiomarkerdiagnosisdifferentially expressed genesprognosisrenal cell carcinoma |
| spellingShingle | Yong Zhang Zhan Chen Jian‐Gang Chen Xin‐Feng Chen Dong‐Hua Gu Zhen‐Min Liu Ya‐Dong Gao Bing Zheng Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma FEBS Open Bio bioinformatics analysis biomarker diagnosis differentially expressed genes prognosis renal cell carcinoma |
| title | Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma |
| title_full | Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma |
| title_fullStr | Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma |
| title_full_unstemmed | Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma |
| title_short | Ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear‐cell renal cell carcinoma |
| title_sort | ceruloplasmin overexpression is associated with oncogenic pathways and poorer survival rates in clear cell renal cell carcinoma |
| topic | bioinformatics analysis biomarker diagnosis differentially expressed genes prognosis renal cell carcinoma |
| url | https://doi.org/10.1002/2211-5463.13283 |
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