J Breast Cancer.  2018 Sep;21(3):288-296. 10.4048/jbc.2018.21.e34.

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

• Kang SH
• Cho J
• Jeong H
• Kwon SY

• KMID: 2421369
• DOI: http://doi.org/10.4048/jbc.2018.21.e34

Abstract

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.

Keyword

Breast neoplasms; Immunohistochemistry; Prognosis; RNA-binding proteins

MeSH Terms

Anoxia
Blotting, Western
Breast Neoplasms*
Breast*
Cell Line
Colonic Neoplasms
Disease-Free Survival
Estrogens
Humans
Hypothermia
Immunohistochemistry
Melanoma
Multivariate Analysis
Ovarian Neoplasms
Phenotype
Prognosis
Prostatic Neoplasms
Receptor, Epidermal Growth Factor
Receptors, Progesterone
RNA-Binding Proteins
Estrogens
RNA-Binding Proteins
Receptor, Epidermal Growth Factor
Receptors, Progesterone

Figure

• 

  Figure 1 Immunohistochemical findings of low RNA-binding motif protein 3 (RBM3) nuclear expression (RBM3≤4). (A, B) No expression of RBM3 in poorly differentiated invasive ductal carcinomas. (C) Weakly expressed RBM3 in invasive micropapillary carcinoma. (D) No expression of RBM3 in moderately differentiated invasive ductal carcinoma (immunohistochemistry for RBM3, ×200).

• 

  Figure 2 Immunohistochemical findings of high RNA-binding motif protein 3 (RBM3) nuclear expression (RBM3>4). (A) Moderately expressed RBM3 in mucinous carcinoma. (B) Strongly expressed RBM3 in well differentiated invasive ductal carcinoma. (C) Strongly expressed RBM3 in classic invasive lobular carcinoma. (D) Moderately expressed RBM3 in metaplastic carcinoma (immunohistochemistry for RBM3, ×200).

• 

  Figure 3 Differences of RNA-binding motif protein 3 (RBM3) protein expression in various human breast cancer cell lines by western blot analysis. RBM3 protein is markedly increased in MCF-7 and T47D (luminal A subtype) and ZR-75-1 (luminal B subtype). On the other hand, RBM3 protein is significantly reduced in HCC1954 (HER2-enriched type) and BT-20 (basal-like subtype).

• 

  Figure 4 The comparison of disease-free survival between patients with high RNA-binding motif protein 3 (RBM3) expression (RBM3>4) and low RBM3 expression (RBM3≤4) in invasive ductal carcinoma.

• 

  Figure 5 The comparison of overall survival between patients with high RNA-binding motif protein 3 (RBM3) expression (RBM3>4) and low RBM3 expression (RBM3≤4) in invasive ductal carcinoma.

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