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Identification of Hub Genes and Pathways With Immune Cell Infiltration in Cholangiocarcinoma by Weighted Gene Co-expression Network Analysis
Sujing Jiang
Department of Radiation and Medical Oncology, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7631-7520
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Cholangiocarcinoma (CCA) is the most frequent tumor in biliary tract and the second most common primary tumor of the liver. However, the molecular biomarkers in tumorigenesis of CCA remain unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and therapeutic targets.
Method: The genes expression sequencing of normal and CCA samples were selected from the Gene Expression Omnibus database (GEO) and the Cancer Genome Atlas (TCGA). The weighted gene co-expression network analysis (WGCNA) was used to build the co-expression network. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for the selected genes. The protein-protein interactions of these modules are visualized using cytoscape. Furthermore, the significance of these genes was confirmed by survival analysis. The tumor immune estimation resource (TIMER) was presented to investigate assess the relationship between the hub genes and the immune cells infiltration.
Results: Ten hub genes with CCA development were identified in this study containing CDC20, CCNA2, TOP2A, AURKA, CCNB2, UBE2C, NUSAP1, PRC1, PTTG1 and MCM4. Key genes of CCNB2 and PTTG1 might be potential prognostic biomarkers for CCA. GO analysis indicated the enrichment terms of nuclear division, collagen-containing extracellular matrix and cell adhesion molecule binding. KEGG analysis demonstrated that the cell cycle pathway was the significantly altered pathway. There was a negative correlation between TOP2A, AURKA, CCNB2, PRC1 expression and the infiltration of CD4+T cell, while MCM4 expression was positively associated with the infiltration of neutrophil cells. No significant association between CDC20 levels and CD4+T cell, CD8+T cell, B cell, neutrophil, macrophage, or dendritic cell infiltration in CCA, the same as CCNA2, UBE2C, NUSAP1, PTTG1 respectively.
Conclusion: These candidate genes may involve in the development of CCA. Our results offer novel insights into the etiology, prognosis, and treatment of CCA.
Keywords
cholangiocarcinoma, weighted gene co-expression network analysis, hub gene, pathway, immune cell infiltration
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Research
Identification of Hub Genes and Pathways With Immune Cell Infiltration in Cholangiocarcinoma by Weighted Gene Co-expression Network Analysis
Sujing Jiang
Department of Radiation and Medical Oncology, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7631-7520
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 29 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Cholangiocarcinoma (CCA) is the most frequent tumor in biliary tract and the second most common primary tumor of the liver. However, the molecular biomarkers in tumorigenesis of CCA remain unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and therapeutic targets.
Method: The genes expression sequencing of normal and CCA samples were selected from the Gene Expression Omnibus database (GEO) and the Cancer Genome Atlas (TCGA). The weighted gene co-expression network analysis (WGCNA) was used to build the co-expression network. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for the selected genes. The protein-protein interactions of these modules are visualized using cytoscape. Furthermore, the significance of these genes was confirmed by survival analysis. The tumor immune estimation resource (TIMER) was presented to investigate assess the relationship between the hub genes and the immune cells infiltration.
Results: Ten hub genes with CCA development were identified in this study containing CDC20, CCNA2, TOP2A, AURKA, CCNB2, UBE2C, NUSAP1, PRC1, PTTG1 and MCM4. Key genes of CCNB2 and PTTG1 might be potential prognostic biomarkers for CCA. GO analysis indicated the enrichment terms of nuclear division, collagen-containing extracellular matrix and cell adhesion molecule binding. KEGG analysis demonstrated that the cell cycle pathway was the significantly altered pathway. There was a negative correlation between TOP2A, AURKA, CCNB2, PRC1 expression and the infiltration of CD4+T cell, while MCM4 expression was positively associated with the infiltration of neutrophil cells. No significant association between CDC20 levels and CD4+T cell, CD8+T cell, B cell, neutrophil, macrophage, or dendritic cell infiltration in CCA, the same as CCNA2, UBE2C, NUSAP1, PTTG1 respectively.
Conclusion: These candidate genes may involve in the development of CCA. Our results offer novel insights into the etiology, prognosis, and treatment of CCA.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7