Clinical Significance of Bromodomain-Containing Protein 9 in Colorectal Cancer

Switch/sucrose nonfermentable (SWI/SNF) complexes regulate gene expression through chromatin remodeling and include a recently reported subtype non-canonical BAF (ncBAF). The BRD9 gene that plays a central role in forming ncBAF has been reported to be a poor prognostic factor for various carcinomas. However, the role of BRD9 in colorectal cancer (CRC) has rarely been explored.

In this study, resected specimens acquired from 124 patients who underwent colorectal resection at our institution between January 2013 and December 2013 were immuno-stained and analyzed.

The BRD9 high-expression groups exhibited poor prognoses in terms of overall and disease-free survival rates; moreover, high expression was identified as an independent prognostic factor via multivariate analysis. The BRD9 knockdown predominantly decreased the migration and proliferation abilities in the human CRC cell line compared with in the negative controls. RNA sequencing suggested the potential association of BRD9 with 13 genes, including CCN1. In a mouse subcutaneous tumor model, the BRD9 knockdown significantly reduced tumorigenesis compared with that in the negative control.

These results indicate that BRD9 is an independent poor prognostic factor in CRC and is involved in tumor proliferation, migration, and tumorigenicity through the CCN1-mediated enhancement of cancer cell malignancy.