High BAP1 expression is associated with poor prognosis in patients with colorectal liver metastases

Abstract

BRCA-1-associated protein 1 (BAP1) is a deubiquitinating enzyme that regulates gene expression. Although previous studies have demonstrated that the role of BAP1 is either tumor promotive or suppressive, depending on the tumor and cell types, the role of BAP1 in colorectal cancer and liver metastases remains unclear. The clinical data of 81 patients who underwent hepatic resection for liver metastases after primary resection of colorectal cancer were analyzed. BAP1 expression in primary tumors and liver metastases was evaluated using immunohistochemistry, and high BAP1 expression was significantly associated with a poor prognosis. High BAP1 expression in liver metastases was an independent prognostic factor for poor overall and disease-free survival. In vitro studies using colon cancer cell lines have demonstrated that BAP1 overexpression increases cell proliferation, migration, invasion, and cancer stem cell-like properties. In contrast, BAP1 knockdown induced the opposite results. Western blot analyses showed that BAP1 overexpression induced the expression of vimentin, MMP2, and MMP9 but decreased E-cadherin expression. Collectively, high BAP1 expression was associated with a significantly poor prognosis in patients with colorectal cancer and liver metastasis by increasing cell proliferation, invasion, migration, and cancer stem cell-like properties.