Immunosuppressive State May Lead to Brain Metastases in Lung Squamous Cell Carcinoma: Gene Expression and Immunohistochemical Analysis

Background/Aim: Brain metastases (BMs) are rare in lung squamous cell carcinoma (LUSC). Therefore, research on biomarkers or mechanisms that can be used to predict them is limited. To verify whether mRNA profiles can accurately predict BMs, we used a machine learning approach on 20 TNM-matched LUSC tissue samples. Materials and Methods: We conducted pathway and immunohistochemical analyses to investigate the underlying mechanisms of BM. Results: A total of 15 mRNAs linked to BM were identified. The 15-mRNA signature was highly accurate in predicting BM, with an area under the curve and accuracy of 0.940 and 0.9, respectively. The pathway analysis revealed that immune-related pathways (leukocyte transendothelial migration, Fc gamma R-mediated phagocytosis, and natural killer cell-mediated cytotoxicity) were suppressed, suggesting that an immunosuppressive state may be involved in the development of BM. In the validation set confirmed by immunohistochemical staining, the BM group exhibited significantly lower levels of CD4+ T cells or CD8+ T cells than the group without BM. BM in patients with LUSC was associated with an immunosuppressive state. Conclusion: Immunotherapy may be effective in preventing BM in patients with LUSC.