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Published online: 2024-04-08

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Higher neoantigen load correlates with better overall survival in Chinese lung adenocarcinoma patients

Xuemei Liu1, Yongfeng Yu1, Wenhui Song2, Xiao Deng2, Kaili Gu2, Mengdi Yuan2, Zeyu Jiang2, Yu Wang2, Yafei Zhang2


Introduction. Neoantigen load (NAL) has been extensively studied as a promising biomarker for immunotherapy. Recently it was also reported that NAL is associated with lung cancer patient survival, but the results were not consistent. 

Material and methods. To further evaluate the prognostic value of NAL in lung cancer, we analyzed NAL in a cohort of 96 lung adenocarcinoma (AD) and 83 lung squamous cell carcinoma (SQ) patients from the Cancer Genome Atlas (TCGA). We found that high NAL correlates with better overall survival (OS) of AD patients but with worse OS of SQ patients. Next, we collected a total of 25 NSCLC patient samples and explored whole exome sequencing (WES) and a large targeted gene panel (Med1CDx panel containing 579 genes) for NAL and tumor mutation burden (TMB) analysis. 

Results. We found that patients with both higher NAL and TMB, who underwent chemotherapy combined with immunotherapy, showed better OS and progression-free survival (PFS) in both AD and SQ subgroups. We also compared the concordance of NAL and TMB between WES and the Med1CDx panel. The R2 for concordance of NAL and TMB prediction by WES and our Med1CDx panel was 0.81 and 0.86, respectively. 

Conclusions. In this study, we showed that NAL is a useful biomarker for lung cancer OS prediction at least in the AD cohort. Furthermore, considering the high cost ofWES, large targeted gene-panel-based NAL and TMB analysis could be a good alternative in clinical practical settings. 

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