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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment
Peng Tang1,2, Gangfu Zheng1, Congcong Xu3
1The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Background:
Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC).
Methods:
We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC.
Results:
The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells.
Conclusion:
ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.
Insights
High NEK2 expression in clear cell renal cell carcinoma (ccRCC) is linked to poor prognosis and increased proliferation. However, it also correlates with higher mutation burden and better response to certain treatments, alongside increased immune cell infiltration.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- NEK2 kinase is crucial for cell cycle regulation and linked to poor prognosis in various cancers.
- Limited research exists on NEK2's role in clear cell renal cell carcinoma (ccRCC).
Purpose of the Study:
- To investigate the role and prognostic significance of NEK2 in ccRCC.
- To explore the relationship between NEK2 expression and clinical outcomes, tumor mutational burden, immune infiltration, and therapeutic response in ccRCC.
Main Methods:
- Utilized clinical, transcriptional, and mutational data from GEO and TCGA databases.
- Performed Gene Ontology and KEGG pathway analyses for NEK2 coexpressed genes.
- Analyzed correlations between NEK2 levels, survival, mutations, immunotherapy response, drug sensitivity, immune cell infiltration, and validated findings with immunofluorescence.
Main Results:
- NEK2 gene is overexpressed in ccRCC, promoting nuclear division and cell cycle progression.
- Higher NEK2 expression correlates with worse clinical outcomes, increased mutation burden, and improved therapeutic response.
- NEK2 overexpression is associated with increased infiltration of various immune cells, including CD8+ T cells and Tregs.
Conclusions:
- NEK2 overexpression in ccRCC patients predicts a poorer prognosis due to enhanced proliferation.
- Increased NEK2 levels are linked to elevated CD8+ T cell and Treg infiltration, T-cell exhaustion, and a better response to specific treatments.
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