Prognosis and immunological role of HLA-DMA in lung adenocarcinoma

Background: HLA-DMA presents pathogen-derived antigens to CD4+ and CD8+ T cells, respectively, and plays a significant part in initiating the immune response. So far, the impact of HLA expression on the prognosis of BC cells is controversial, because few studies have shown that the expressions of some HLA genes are related to the improvement of the survival rate. Up till now, however, the relationship between HLA-DMA and LUAD has not yet been assessed. Methods: We analyzed the TCGA database and assessed the prognostic value of HLA-DMA in LUAD. We conducted the Kruskal-Wallis and Wilcoxon signed-rank test and utilized logistic regression to assess the role of clinical-pathologic characteristics and HLA-DMA expression. Kaplan-Meier method and the multivariate and univariate Cox regression were also used for evaluating the prognosis-related factors of LUAD. GSEA was used to identify HLA-DMA-related key pathways. The ssGSEA of the TCGA data was used to investigate the correlations between HLA-DMA and cancer immune cell infiltration. Results: Low HLA-DMA expression was related to poorer disease-specific survival (DSS) and overall survival (OS) of LUAD patients. GSEA revealed that HLA-DMA was tightly interrelated with an immune response by the reactome activation of anterior hox genes in hindbrain development during the early embryogenesis signaling pathway. The expression of HLA-DMA was positively associated with cytotoxic cell infiltration and negatively related to the Th2 cell infiltration according to the ssGSEA. Western blotting and the CCK-8 assay showed that KD-HLA-DMA could significantly increase the proliferation of A549 cells and significantly reduce cell pyroptosis. Conclusion: All the observations implied that HLA-DMA was associated with patient prognosis and immune infiltration in LUAD.