Abstract

Background: This study aimed to examine the effects of BIRC5 on the clinical and tumor micro environmental aspects of Lung Adenocarcinoma (LUAD), as well as its predictive and prognostic qualities, given its vital function in carcinogenesis, recurrence and chemoresistance.

Methods: Analysis was conducted on the transcriptome and clinical data of 535 LUAD samples, 59 normal lung samples and 54 patients who were treated with Immune Checkpoint Blockades (ICB) for Non-Small Cell Lung Cancer (NSCLC). To determine the correlation between BIRC5 expression level and tumor micro environmental characteristics, deconvolution analysis was performed. The Log-rank test and Cox regression analysis were also utilized to assess the prognostic and predictive values of BIRC5.

Results: BIRC5 expression was significantly greater in LUAD than in normal lung tissues. Adverse clinical outcomes were significantly correlated with higher BIRC5 expression. Analysis of transcriptome and single-cell sequencing data showed a correlation between various pathways' enrichment and tumors exhibiting high BIRC5 expression. Deconvolution analysis revealed a positive link between BIRC5 expression and regulatory T cells (Tregs) infiltrations, but a negative correlation between BIRC5 expression and CD8⁺ T cell, dendritic cell and NK cell infiltration levels in LUAD. Significantly, ICB with high BIRC5 expression was given to NSCLC patients and these patients had significantly lower overall survival (3.1 vs. 12.7 months; p=0.005) and progression-free survival (1.2 vs. 4.5 months; p=0.012) than those with low BIRC5 expression.

Conclusion: 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.

Keywords: Non-small cell lung cancer; Bioinformatics; BIRC5; TME; Immunotherapy