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Dan Yan
Jinhua Municipal Central Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4336-9153
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Background Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. And many studies have revealed high-TMB may be significantly associated with response to PD-1 and PD-L1 blockade immunotherapy.
Methods The RNA-seq transcriptome profiling, simple nucleotide variation and corresponding clinicopathological information of patients with lung squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA). We classified samples into the low-TMB group and the high-TMB group based on somatic mutation data from TCGA. KEGG pathways analysis was used to analyze the enriched pathways between two groups. Wilcoxon test was used to analyze the correlation between TMB and clinical pathology. CIBERSORT was used to calculate the immune cell infiltration among different risk groups.
Result Single nucleotide polymorphism (SNP), missense mutation and C > A was most common in patients with lung squamous cell carcinoma. Top 10 most common mutated genes were TTN, TP53, MUC16, CSMD3, RYR2, LRP1B, USH2A, SYNE1, ZFHX4, KMT2D. High-TMB group conferred better one-year overall survival. KEGG pathways analysis revealed that DEGs were mainly involved in regulation of lymphocyte activation, lymphocyte proliferation, leukocyte proliferation and mononuclear cell proliferation. Infiltration levels of CD8 + T cell, M1 macrophages, follicular helper T cells and activated NK cells in high-TMB group were higher than that in low-TMB group.
Conclusion High TMB correlated with positive one-year survival outcomes. With the development of tumor, TMB increased gradually. TMB might influence the immune infiltrates on patients with lung squamous cell carcinoma.
Keywords
Tumor Mutation Burden (TMB), Immune microenvironment, Lung squamous cell carcinoma
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Dan Yan
Jinhua Municipal Central Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-4336-9153
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 19 Nov, 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 Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. And many studies have revealed high-TMB may be significantly associated with response to PD-1 and PD-L1 blockade immunotherapy.
Methods The RNA-seq transcriptome profiling, simple nucleotide variation and corresponding clinicopathological information of patients with lung squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA). We classified samples into the low-TMB group and the high-TMB group based on somatic mutation data from TCGA. KEGG pathways analysis was used to analyze the enriched pathways between two groups. Wilcoxon test was used to analyze the correlation between TMB and clinical pathology. CIBERSORT was used to calculate the immune cell infiltration among different risk groups.
Result Single nucleotide polymorphism (SNP), missense mutation and C > A was most common in patients with lung squamous cell carcinoma. Top 10 most common mutated genes were TTN, TP53, MUC16, CSMD3, RYR2, LRP1B, USH2A, SYNE1, ZFHX4, KMT2D. High-TMB group conferred better one-year overall survival. KEGG pathways analysis revealed that DEGs were mainly involved in regulation of lymphocyte activation, lymphocyte proliferation, leukocyte proliferation and mononuclear cell proliferation. Infiltration levels of CD8 + T cell, M1 macrophages, follicular helper T cells and activated NK cells in high-TMB group were higher than that in low-TMB group.
Conclusion High TMB correlated with positive one-year survival outcomes. With the development of tumor, TMB increased gradually. TMB might influence the immune infiltrates on patients with lung squamous cell carcinoma.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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