Abstract | BACKGROUND: The aim of the study was to investigate differences in HLA-I alleles between lung adenocarcinoma patients and healthy controls and determine their association with PD-L1 expression and tumor mutational burden (TMB) to understand the mechanism underlying lung adenocarcinoma susceptibility. METHODS: Differences in HLA allele frequencies between the two groups were analyzed in a case-control study. PD-L1 expression and TMB in lung adenocarcinoma patients were determined and their relationships with HLA-I were analyzed. RESULTS: The lung adenocarcinoma group showed significantly higher HLA-A*30:01 (p = 0.0067, odds ratio [OR], 1.834; 95% confidence interval [CI]: 1.176-2.860), B*13:02 (p = 0.0050, OR, 1.855; 95% CI: 1.217-2.829), and C*06:02 (p = 0.0260, OR, 1.478; 95% CI: 1.060-2.060) and significantly lower B*51:01 (p = 0.0290, OR, 0.6019; 95% CI: 0.3827-0.9467), and C*14:02 (p = 0.0255, OR, 0.5089; 95% CI: 0.2781-0.9312) than the control group. Haplotype analysis results showed that HLA-A*30:01-B*13:02 (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085), A*11:01-C*01:02 (p = 0.0056, OR, 1.909; 95% CI: 1.182-3.085), A*30:01-C*06:02 (p = 0.0111, OR, 1.846; 95% CI: 1.147-2.969), and B*13:02-C*06:02 (p = 0.0067, OR, 1.846; 95% CI: 1.147-2.969) frequencies significantly increased and B*51:01-C*14:02 (p = 0.0219, OR, 0.490; 95% CI: 0.263-0.914) frequency significantly decreased in lung adenocarcinoma patients. Three-locus haplotype analysis showed that HLA-A*30:01-B*13:02-C*06:02 frequency (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085) significantly increased in patients. CONCLUSION:
HLA-A*30:01, B*13:02, and C*06:02 may be the susceptibility genes and HLA-B*51:01 and C*14:01 act as the resistance genes of lung adenocarcinoma. The changes in HLA-I allele frequencies had no association with PD-L1 expression and TMB among these patients.
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Authors | Xuanpeng Wu, Hao Wang, Fei Xue, Tao Jiang, Nanzheng Chen, Tianju Wang, Yong Zhang, Guangjian Zhang, Junke Fu, Qifei Wu |
Journal | Thoracic cancer
(Thorac Cancer)
Vol. 14
Issue 20
Pg. 1932-1940
(Jul 2023)
ISSN: 1759-7714 [Electronic] Singapore |
PMID | 37246469
(Publication Type: Journal Article)
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Copyright | © 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. |
Chemical References |
- B7-H1 Antigen
- Biomarkers, Tumor
- HLA-A Antigens
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Topics |
- Humans
- Adenocarcinoma of Lung
(genetics)
- Alleles
- B7-H1 Antigen
(metabolism)
- Biomarkers, Tumor
(genetics)
- Carcinoma, Non-Small-Cell Lung
(pathology)
- Case-Control Studies
- HLA-A Antigens
(genetics)
- Immunotherapy
(methods)
- Lung Neoplasms
(pathology)
- Mutation
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