Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
*These authors contributed equally to this work.
Background: Lung adenocarcinoma (LUAD) is the most prevalent thoracic cancer with the highest incidence and mortality worldwide. Baculoviral IAP Repeat Containing 5 (BIRC5) is well studied in many malignancies, its prognosis value and correlation with the tumor microenvironment (TME) in LAUD remains largely elusive.
Methods: The Wilcoxon signed-rank test and logistic regression were used to evaluate the relationship between clinical features and BIRC5 expression in LUAD. To assess the impact of BIRC5 on prognosis, the Kaplan-Meier plotter analysis and Cox regression were used, as well as a receiver operating characteristic (ROC) curve and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were recruited to predict the association between BIRC5 and immune cell infiltrations. Furthermore, qRT-PCR and western bolt were utilized to confirm gene expression on mRNA and protein levels. The proliferation of A549 and H1299 cells was evaluated using CCK8 and EdU assay. Cell mobility was tested by transwell assay and wound healing assay. Detection of PD-L1 and infiltrated CD8 T cells in xenograft tumors was done by flow cytometry.
Results: BIRC5 expression was found to be substantially greater in LUAD patients. According to KM-plotter analysis, patients with high levels of BIRC5 had shorter survival rates. Multivariate Cox analysis revealed that elevated BIRC5 expression was an independent risk factor for OS and PFS in LUAD patients. High BIRC5 expression was predicted to be associated with chemokine activity and immune cell chemotaxis, whereas ssGSEA suggested that BIRC5 is highly associated with CD8 T cell infiltration and PD-L1 levels. In vitro experiments suggested overexpression of BIRC5 promoted the proliferation, mobility, and PD-L1 level of A549 cells, and vice versa in H1299 cells. Furthermore, in vivo study suggested elevated tumor weight and PD-L1 levels in xenograft tumors generated from LLC cells with overexpressed BIRC5.
Conclusion: BIRC5 promotes lung adenocarcinoma progression by modulating PD-L1 expression and inducing tumor immune evasion.
Keywords: LUAD, BIRC5, PD-L1, Immune infiltration