Tumor Suppressor Effect of RBMS3 in Breast Cancer

Abstract

Background: RBMS3 (RNA-binding motif, single-stranded-intervacting protein 3) acts as a tumor-suppressive gene in a number of human cancers, however, its role in breast cancer is not fully understood. This study aimed to investigate the expression and clinicopathological significance of RBMS3 in breast cancer. Methods: A total of 998 breast cancer tissue samples in The Cancer Genome Atlas (TCGA) database with survival outcomes were divided into high RBMS3 expression and low expression groups using the median as the cutoff. Clinicopathological characteristics and prognosis were compared between the 2 groups. Results: TCGA showed that RBMS3 mRNA was downregulated in breast cancer tissues, and RBMS3 downregulation was correlated with poor prognosis. Immunohistochemistry staining of 127 paraffin-embedded breast cancer tissues showed that RBMS3 protein was localized in the cytoplasm and nucleus; however, nuclear staining was present in 90.0% of normal breast tissues but only 28.3% of breast cancer tissues. Decreased RBMS3 protein expression was significantly correlated with estrogen receptor (ER)-negative status and death at final follow-up. Patients with lower RBMS3 protein expression had substantially shorter survival than those with higher RBMS3 expression. Univariate and multivariate analysis indicated that the combination of RBMS3 expression and ER status (a variable designated as “cofactor”) was an independent prognostic factor in patients with breast cancer (hazard ratio [HR] = 0.420, 95% confidence interval [CI]: 0.223-0.791, P = 0.007). Conclusion: RBMS3 downregulation was correlated with poor prognosis in breast cancer patients, and the combination of RBMS3 expression and ER status was an independent prognostic factor.