BIRC5 expression correlated with immunosuppressive phenotype and predicted inferior response to immunotherapy in lung adenocarcinoma

Abstract

Background Considering the pivotal role of BIRC5 in tumorigenesis, recurrence, and chemoresistance, this study aimed to investigate its impact on the clinical and tumor microenvironmental features of lung adenocarcinoma (LUAD), together with its predictive and prognostic values. Methods Clinical and transcriptomic data of 535 LUAD samples, 59 normal lung, and 54 patients with non-small-cell lung cancer (NSCLC) received immune checkpoint blockades (ICB) were analyzed. Deconvolution analysis was conducted to uncover the relationship between tumor microenvironmental features and BIRC5 expression level. The predictive and prognostic values of BIRC5 was also evaluated with Log-rank test and Cox regression analysis. Results LUAD had a significantly higher BIRC5 expression level than normal lung tissues. The elevated BIRC5 expression was markedly associated with unfavorable clinical outcomes. Transcriptomic and single-cell sequencing data analysis revealed that tumors with high BIRC5 expression was correlated with multiple pathways’ enrichment. Deconvolution analysis indicated a negative correlation between BIRC5 expression and infiltration levels of CD8 + T cells, dendritic cells, and NK cells in LUAD, but a positive correlation was observed between BIRC5 expression and regulatory T cells (Tregs) infiltrations. Importantly, NSCLC patients received ICB with high BIRC5 expression had dramatically shorter progression-free (1.2 vs. 4.5 months; P = 0.012) and overall survival (3.1 vs. 12.7 months; P = 0.005) than those with low BIRC5 expression. Conclusions These findings suggested that high BIRC5 expression was associated with DNA damage/repair, cell invasion and proliferation related pathways enrichment and increased Tregs infiltration, which would result in inferior outcomes in NSCLC received ICB.