Loss of ARID1A/BAF250a expression is linked to tumor progression and adverse prognosis in cervical cancer

Abstract

The tumor suppressor gene ARID1A encodes BAF250a, a component of human SWI/SNF chromatin-remodeling complexes. Loss of BAF250a expression has recently been reported in several tumor types. To investigate the potential correlation between BAF250a and various clinicopathologic parameters, we assessed the expression of BAF250a in archival tumor tissue specimens from 147 patients with cervical cancer and 191 with cervical intraepithelial neoplasia as well as 376 matched nonadjacent normal tissues by immunohistochemical staining. Messenger RNA expression level for BAF250a was decreased in cervical cancer cell lines (P = .013) and tissues (P = .010), when compared with normal cervical epithelial tissue using SYBR Green real-time polymerase chain reaction. BAF250a was also detected in nuclear fractions of HeLa cells and in nuclei of cervical cancer tissue samples by Western blotting and immunohistochemistry, respectively. BAF250a expression gradually decreased in transitioning from normal to cervical carcinoma (P < .001), and this loss of expression was significantly associated with tumor stage (P = .005), tumor grade (P = .029), tumor size (P = .003), and lymph node metastasis (P = .020). In multivariate analysis, overall survival in cervical cancer was significantly reduced in cases with BAF250a loss (hazard ratio, 2.78 [1.01-7.63]; P = .047). Our findings suggest a potential role for BAF250a in providing valuable prognostic information to clinicians for risk assessment in cervical cancer.