High Expression Level of BRD4 Is Associated with a Poor Prognosis and Immune Infiltration in Esophageal Squamous Cell Carcinoma.

Background: Bromodomain-containing protein 4 (BRD4) is a reader of histone acetylation and is associated with a variety of diseases.

Aim: To investigate the expression level of BRD4 in esophageal squamous cell carcinoma (ESCC), its prognostic value and its relationship with immune infiltration.

Methods: The study included 94 ESCC patients from The Cancer Genome Atlas (TCGA) database and 179 ESCC patients from Affiliated Hospital 2 of Nantong University. The expression levels of proteins in tissue microarray were detected by immunohistochemistry. The prognostic factors were analyzed by Kaplan-Meier curve and univariate and multivariate cox regression. The ESTIMATE website was used to calculate the stromal, immune and ESTIMATE score. CIBERSORT was used to calculate the abundance of immune infiltrates. Spearman and Phi coefficient were used for correlation analysis. The TIDE algorithm was used to predict treatment response to immune checkpoint blockade.

Results: BRD4 is up-regulated in ESCC, and high BRD4 expression level is associated with poor prognosis and adverse clinicopathological features. In addition, the monocyte count, systemic inflammatory-immunologic index, platelet-lymphocyte ratio, and monocyte-lymphocyte ratio in the BRD4 high expression level group were higher than in the low expression level group. Finally, we found that BRD4 expression level correlated with immune infiltration and that it was inversely correlated with infiltration of CD8 + T cells. Higher TIDE scores in the BRD4 high expression group than in the low expression group.

Conclusion: BRD4 is associated with poor prognosis and immune infiltration in ESCC, and may be a potential biomarker for prognosis and immunotherapy application.