CXCL8 is a prognostic biomarker and correlated with TNBC brain metastasis and immune infiltration

Patients with TNBC are associated with an increased risk of developing brain metastasis and shortest median survival post-brain metastasis-diagnosis. However, the regulatory mechanism of TNBC brain metastasis has not been addressed. Here, by a series of integrated analyses of differential gene expression profile from brain metastases and primary triple negative breast cancer, we identified 15 differentially expressed genes in both TNBC brain metastasis tissue samples and TNBC brain metastasis cell line. After analyzing the prognostic value of those 15 differentially expressed genes, we found that CXCL8 was the only gene associated with multiple prognostic indicators in both all-breast cancer and TNBC populations. Functional and pathway enrichment analyses demonstrated that CXCL8 was associated with humoral immune response and immune cell infiltration. CXCL8 expression had a positive correlation with three immune-related scores (ImmuneScore, ESTIMATEScore and StromalScore), and multiple types of immune cell infiltration, including macrophages, neutrophils and Th1 cells. Besides, we also verified the prometastatic effect of CXCL8, by treating MDA-MB-231 and Hs578t cells with different concentrations of recombinant human CXCL8. Taken together, our results suggest that CXCL8 can be used as a prognostic biomarker and is associated with TNBC brain metastasis and immune infiltration. Our findings provide a new perspective on TNBC brain metastasis and illustrate great potential to develop new CXCL8-targeted therapy for clinical TNBC patients.