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.