Abstract
Background
The incidence of lung cancer tends to be younger, and adenocarcinoma is the main histological type. Even patients with the same tumor type may have significant differences in clinical features, tumor microenvironment and genomic background at different ages. Immune checkpoint inhibitors (ICIs) have been shown to improve clinical outcomes in patients with lung adenocarcinoma (LUAD). However, differences in ICI efficacy between older and younger patients are unknown. Our study aimed to explore the relationship between age and immunotherapy in LUAD.
Methods
In our study, 1313 resected LUAD patients in our hospital were divided into young (age ≤ 50) and old groups (age > 50), and the clinical characteristic differences between them were analyzed. Of these, next-generation sequencing (NGS) was performed on the 311 cases. In addition, immune-related signatures of 508 LUAD patients were analyzed by TCGA RNA expression data. Then, we validated genomic and clinical information of 270 LUAD samples in the MSKCC cohort.
Results
ERBB2 and EGFR gene mutations were significantly different between the two groups, and the gene mutation number in the old group was significantly higher than that in the young group. In addition, immune-related signatures of LUAD patients were analyzed by TCGA RNA expression data, which indicated that the patients in the old group might have a better immune microenvironment. Then, we validated the MSKCC cohort and found that the TMB of the old group was significantly higher than that of the young group, and the OS of immunotherapy was longer in the old group.
Conclusion
Our study was the first to analyze the differences in the genomic landscape and immune-related biomarkers between the young and old groups of LUAD patients and found that the old group had a better efficacy of immunotherapy, providing a reference for the study design and treatment of patients with LUAD.
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Availability of data and materials
The datasets generated during and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank Mr. Qin Zhang, Mr. Hao Guo, Mr. Wang-Long Deng, Mr. Guang-Hua Lu, Mr. Ran Ding, Ms. Qin Shuai and Ms. Fei Wang from Simceredx for the kindly assistance.
Funding
This work was supported by following grants: WU JIEPING Medical Foundation (No. 320.6750.2021-01-4).
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YJW, PL, and SYC planed the study. YXQ, NNL, XFZ, and MHG analyzed data and interpreted the results. PL, QJL, YPX, and JLL enrolled the patients, involved in the patients’ treatment and collected the clinical data. YXQ, NNL, XFZ, and MML wrote the manuscript. YJW, TTS, and CQ participated in manuscript revision and editing. All authors read and approved the final manuscript.
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Supplementary file1. Fig. S1. KEGG and GO enrichment of gene mutations in the different groups. A KEGG enrichment for the genomic alteration results of 311 LUAD patients using a 224-gene panel. B GO enrichment for the genomic alteration results of 311 LUAD patients using a 224-gene panel. (DOCX 408 KB)
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Li, P., Che, S., Qi, Y. et al. Age-dependent genomic characteristics and their impact on immunotherapy in lung adenocarcinoma. J Cancer Res Clin Oncol 149, 2997–3007 (2023). https://doi.org/10.1007/s00432-022-04195-8
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DOI: https://doi.org/10.1007/s00432-022-04195-8