High expression level of BRD4 is associated with a poor prognosis and immune infiltration in esophageal squamous cell carcinoma

Abstract Purpose The aim of this study is to evaluate the expression level of Bromodomain-containing protein 4 (BRD4), its prognostic value, and its relationship with immune infiltration in esophageal squamous cell carcinoma (ESCC). Methods The study included 80 ESCC patients from The Cancer Genome Atlas (TCGA) database and 179 ESCC patients from Affiliated Hospital 2 of Nantong University. The expression levels of BRD4 and CD8 in tissue microarray were detected by immunohistochemistry. The prognostic factors affecting overall survival of ESCC 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 and XCELL were 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 (SII), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in the BRD4 high expression level group were higher than those in the low expression level group. Finally, we found that BRD4 expression level correlated with immune infiltration and that BRD4 expression level was inversely correlated with infiltration of CD8+T cells. In the TCGA esophageal cancer cohort, the BRD4 high expression level group had a higher TIDE score than the low expression level group. The same trend was observed in the TCGA ESCC cohort, but the P value was 0.058. Conclusion BRD4 is associated with poor prognosis and immune infiltration in ESCC, and may be a potential biomarker for prognosis and immunotherapy application.