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Volume 27, Issue 18
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Immunotherapy has been a promising treatment in advanced lung cancer. However, only a few patients could benefit from it. Herein, we aimed to explore mutation-related predictive biomarkers in lung squamous cell carcinoma (LUSC), which could help develop clinical immunotherapy strategies and screen beneficial populations.

Methods

Co-occurrence and mutually exclusive analysis was conducted on the TCGA-LUSC cohort. Correlations between the gene mutation status and tumor mutation burden (TMB) levels, and neo-antigen levels were analyzed by Wilcoxon test. Kaplan-Meier method was employed to analyze the progression-free survival (PFS) of lung cancer patients with immunotherapy. Gene set enrichment analysis (GSEA) was used to investigate the functional changes affected by TP53mut/TTNmut. The immune cell infiltration landscape in co-mutation subgroups was analyzed using CIBERSORT.

Results

1) TP53, TTN, CSMD3, MUC16, RYR2, LRP1B, USH2A, SYNE1, ZFHX4, FAM135B, KMT2D, and NAV3 were frequently mutated in LUSC patients. 2) TMB levels in highly mutated groups were higher than that in wild type groups. 3) There were higher neo-antigen levels in mutation group compared to the wild-type group, and LUSC patients in mutation group had longer PFS. 4) TP53mut/TTNmut co-mutation group exhibited higher TMB levels and better response to immunotherapy. 5) A host of immune-related signaling pathways was inhibited in TP53mut/TTNmut subgroup. 6) There were more T follicular helper cells and NK cells were in TP53mut/TTNmut subgroup than in the WT subgroup.

Conclusion

The LUSC patients with TP53 and TTN co-mutation had higher TMB levels and better response to immunotherapy. The TP53 and TTN co-mutation is a promising novel biomarker to assist LUSC immunotherapy evaluation.

© 2024 Bentham Science Publishers
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2023-10-23
2025-01-12

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Co-mutation of TP53 and TTN is Correlated with the Efficacy of Immunotherapy in Lung Squamous Cell Carcinoma
Comb Chem High Throughput Screen 27, 2699 (2024); https://doi.org/10.2174/0113862073246841230922052004
/content/journals/cchts/10.2174/0113862073246841230922052004
/content/journals/cchts/10.2174/0113862073246841230922052004
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  • Article Type:     Research Article
Keyword(s): 53 (TP53); immunotherapy response; Lung squamous cell carcinoma (LUSC); mutation; TMB; tumor protein

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