High RNA-binding Motif Protein 3 Expression Is Associated with Improved Clinical Outcomes in Invasive Breast Cancer

PURPOSE: Expression of RNA-binding motif protein 3 (RBM3) is induced by hypoxia and hypothermia. Recently, high expression of RBM3 was reported to be associated with a good prognosis in colon cancer, prostate cancer, ovarian cancer, and malignant melanoma. Studies on RBM3 in invasive breast carcinoma (IBC), however, are limited. METHODS: RBM3 expression was examined using a tissue microarray from 361 patients with IBC. Immunohistochemistry was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 to compare the expression of these markers. For scoring of RBM3 expression, NF (nuclear staining fraction)×NI (nuclear staining intensity) was used. The RBM3 expression score was considered indicative of either low (≤4) or high (>4) expression. Western blot analysis was performed on breast cancer cell lines to evaluate RBM3 expression. RESULTS: Of the total 361 samples, 240 (66.5%) exhibited high RBM3 expression. High RBM3 expression was significantly associated with positivity for ER (p<0.001), PR (p<0.001), T stage (p<0.001), histologic grade (p<0.001), and % Ki-67 staining (p=0.004). Multivariate analysis revealed that high RBM3 expression was closely associated with prolonged disease-free survival (DFS) (p<0.001) and overall survival (OS) (p<0.001). Western blot analysis revealed reduced RBM3 expression in HCC1954 (HER2-enriched) and BT-20 (basal-like) cells with an aggressive phenotype. CONCLUSION: High nuclear RBM3 expression is strongly associated with a prolonged DFS and OS. Furthermore, RBM3 expression is closely associated with good prognostic markers such as ER and PR in IBC. High nuclear RBM3 expression is, therefore, a critical biomarker of favorable clinical outcomes in IBC.