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Research
The associations of SNF5 with prognosis and immune responses in bladder cancer
Zhiwen Chen
Department of Urology, Urology Institute of People’s Liberation Army, Southwest Hospital, Army Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9535-2030
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Bladder cancer (BC) is the second most common malignancy in the urinary system. Improving survival has been hampered by high heterogeneity and drug resistance. SNF5, a subunit of the SWI/SNF chromatin-remodeling complex, is commonly lost or inactivated in multiple malignancies. The role of SNF5 in bladder cancer has not yet been elucidated. This is the first exploration into the associations of SNF5 with prognosis and its functions in BC.
Methods
Using datasets from The Cancer Genome Atlas projects and our institution, we investigated the predictive value of SNF5 in bladder cancer, as well as the relationships with clinical characteristics. The differential genes expression analysis, gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) were performed to investigate the functions of SNF5. The Immune Cell Abundance Identifier (ImmuCellAI) algorithm was used to infer the fractions of tumor-infiltrating lymphocytes (TILs). Next, we conducted gene set variation analysis (GSVA) and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to assess the effects of SNF5 on antitumor response and sensitivity to immune checkpoint blockade (ICB).
Results
SNF5 had the potential to predict bladder cancer and a negative correlation with survival. SNF5 was involved in immune response. Low expression of SNF5 promoted infiltration of immune cells into tumor, enhanced the abilities to process and present antigens by activating the MHC-T cell receptor activation pathway. Moreover, decreased SNF5 activated CTLA-4 pathway, upregulating CTLA-4 expression, but SNF5 did not modify the expression of PD-1 or PD-L1. A higher TIDE score was generated in the low-expression group, which indicated that patients with low expression might derive greater benefit from ICB.
Conclusions
Our findings indicated that SNF5 was not only a good biomarker for diagnosis and prognosis of BC, but a potential new target in the immunotherapy for BC.
Keywords
Bladder cancer, TCGA, Tumor-infiltration, Immune cells, Immune checkpoints
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This is a preprint. It has not completed peer review.
Research
The associations of SNF5 with prognosis and immune responses in bladder cancer
Zhiwen Chen
Department of Urology, Urology Institute of People’s Liberation Army, Southwest Hospital, Army Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9535-2030
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 20 May, 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
Bladder cancer (BC) is the second most common malignancy in the urinary system. Improving survival has been hampered by high heterogeneity and drug resistance. SNF5, a subunit of the SWI/SNF chromatin-remodeling complex, is commonly lost or inactivated in multiple malignancies. The role of SNF5 in bladder cancer has not yet been elucidated. This is the first exploration into the associations of SNF5 with prognosis and its functions in BC.
Methods
Using datasets from The Cancer Genome Atlas projects and our institution, we investigated the predictive value of SNF5 in bladder cancer, as well as the relationships with clinical characteristics. The differential genes expression analysis, gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) were performed to investigate the functions of SNF5. The Immune Cell Abundance Identifier (ImmuCellAI) algorithm was used to infer the fractions of tumor-infiltrating lymphocytes (TILs). Next, we conducted gene set variation analysis (GSVA) and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to assess the effects of SNF5 on antitumor response and sensitivity to immune checkpoint blockade (ICB).
Results
SNF5 had the potential to predict bladder cancer and a negative correlation with survival. SNF5 was involved in immune response. Low expression of SNF5 promoted infiltration of immune cells into tumor, enhanced the abilities to process and present antigens by activating the MHC-T cell receptor activation pathway. Moreover, decreased SNF5 activated CTLA-4 pathway, upregulating CTLA-4 expression, but SNF5 did not modify the expression of PD-1 or PD-L1. A higher TIDE score was generated in the low-expression group, which indicated that patients with low expression might derive greater benefit from ICB.
Conclusions
Our findings indicated that SNF5 was not only a good biomarker for diagnosis and prognosis of BC, but a potential new target in the immunotherapy for BC.
Figure 1
Figure 2
Figure 3
Figure 4