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- Title
Combination of Tumor Mutational Burden and Specific Gene Mutations Stratifies Outcome to Immunotherapy Across Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.
- Authors
Peng, Ying-Peng; Wang, Rong; Liu, Qiao-Dan; Xu, Xi-Wei; Wei, Wei; Huang, Xiao-Tao; Peng, Xiao-Mou; Liu, Zhi-Gang
- Abstract
Purpose: To investigate the prognostic significance of tumor mutational burden (TMB) combined with specific prognosis-related gene mutations in immunotherapy for recurrent and metastatic head and neck squamous cell carcinoma (r/m HNSCC). Methods: One hundred thirty-two r/m HNSCC patients from the Morris and Allen cohorts had undergone immunotherapy. We constructed the immunotherapy-related gene prognostic index TP-PR combining TMB and PIK3CA , TP53 , or ROS1 mutation. And we analyzed the differences in overall survival (OS) and immune cell infiltration between samples in different groups. The association of each signature's single-sample gene set enrichment analysis scores with TP-PR was tested using Spearman's correlation test. Results: The median OS of the patients with high TMB (TMB ≥10 mut/Mb) who received immunotherapy for r/m HNSCC was 2.5 times as long as that of the patients with low TMB (25 vs. 10 months). More importantly, the high TP-PR (TP-PR >0) group had better median OS (25 vs. 8 months) than the low TP-PR (TP-PR ≤0) group. CD8+ T cells and activated memory CD4+ T cells in the tissues of the patients with high TP-PR were higher than those in the patients with low TP-PR. Results showed that TP-PR stratification had a higher area under the curve (AUC) value (0.77, 95% CI 0.86–0.68) compared with TMB stratification (0.56, 95% CI 0.68–0.44). The differential gene expression in the high and low TP-PR groups mainly influenced metabolism-related signaling pathways. Conclusion: TP-PR was an effective predictor of immunotherapy outcome for r/m HNSCC, which might be better than TMB alone. Patients with high TP-PR had a better survival benefit than had the patients with low TP-PR.
- Subjects
SQUAMOUS cell carcinoma; IMMUNOLOGIC memory; GENETIC mutation; NECK; CELLULAR signal transduction; OVERALL survival
- Publication
Frontiers in Genetics, 2021, Vol 12, p1
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2021.756506