Correlation of tumor mutational burden with prognosis and immune infiltration in lung adenocarcinoma

Frontiers in Oncology

Oncology

Junyu Li¹  Lin Li² 

[1] Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China;Jiangxi Health Committee Key (JHCK) Laboratory of Tumor Metastasis, Jiangxi Cancer Hospital, Nanchang, China;Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang, China;

关键词: lung adenocarcinoma;    tumor mutation burden;    immune checkpoint blockade;    the cancer genome atlas;    cell proliferation;   

DOI  :  10.3389/fonc.2023.1128785

 received in 2022-12-21, accepted in 2023-02-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundTumor mutational burden (TMB) plays an important role in the evaluation of immunotherapy efficacy in lung adenocarcinoma (LUAD).ObjectiveTo improve the clinical management of LUAD by investigating the prognostic value of TMB and the relationship between TMB and immune infiltration.MethodsTMB scores were calculated from the mutation data of 587 LUAD samples from The Cancer Genome Atlas (TCGA), and patients were divided into low-TMB and high-TMB groups based on the quartiles of the TMB score. Differentially expressed genes (DEGs), immune cell infiltration and survival analysis were compared between the low-TMB and high-TMB groups. We queried the expression of genes in lung cancer tissues through the GEPIA online database and performed experimental validation of the function of aberrant genes expressed in lung cancer tissues.ResultsWe obtained sample information from TCGA for 587 LUAD patients, and the results of survival analysis for the high- and low- TMB groups suggested that patients in the high-TMB group had lower survival rates than those in the low-TMB group. A total of 756 DEGs were identified in the study, and gene set enrichment analysis (GSEA) showed that DEGs in the low-TMB group were enriched in immune-related pathways. Among the differentially expressed genes obtained, 15 immune-related key genes were screened with the help of ImmPort database, including 5 prognosis-related genes (CD274, PDCD1, CTLA4, LAG3, TIGIT). No difference in the expression of PDCD1, CTLA4, LAG3, TIGIT in lung cancer tissues and differential expression of CD274 in lung cancer tissues.ConclusionsThe survival rate of LUAD patients with low TMB was better than that of LUAD patients with high TMB. CD274 expression was down regulated in human LUAD cell lines H1299, PC-9, A549 and SPC-A1, which inhibited malignant progression of A549 cells.

【 授权许可】

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