Frequency changes in HLA‐I alleles: A marker to guide immunotherapy in lung adenocarcinoma patients and its relationship with tumor mutational burden and PD‐L1 expression

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.