Fei Shao1,2, Tiantian Guo1, Pei Jou Chua1, Lili Tang2, Aye Aye Thike3, Puay-Hoon Tan3, Boon Huat Bay1, Gyeong Hun Baeg1. 1. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. 3. Department of Pathology, Singapore General Hospital, Singapore.
Abstract
AIMS: Identification of prognostic and predictive biomarkers for breast cancer is essential to better stratify patients for treatment and evaluate patient outcome. AT-rich interactive domain-containing protein 1B (ARID1B) is implicated in cell proliferation, but its role in tumorigenesis remains unclear. METHODS AND RESULTS: Immunohistochemical analysis of ARID1B expression using breast cancer tissue microarrays containing 156 breast invasive ductal carcinoma patient samples and subsequent statistical data analysis based on ARID1B immunoreactivity score were performed to examine the correlation between clinicopathological parameters in breast cancer and ARID1B expression. In-vitro assays were also performed to study the role of ARID1B in cell cycle progression. Univariate analysis revealed that high ARID1B expression is correlated closely with histological grade (P = 0.045) and size (P = 0.043) of invasive breast cancer. These findings were confirmed by multivariate analysis. Notably, increased ARID1B expression was frequently detected in the aggressive triple-negative breast cancer subtypes (P = 0.039) and associated with decreased 5-year disease-free survival rate. Lastly, MDA-MB-231 cells with reduced ARID1B activity displayed a delay in G1 to S phase cell cycle transition and consequently showed a decrease in cell proliferation compared with controls (P < 0.001). CONCLUSIONS: ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer.
AIMS: Identification of prognostic and predictive biomarkers for breast cancer is essential to better stratify patients for treatment and evaluate patient outcome. AT-rich interactive domain-containing protein 1B (ARID1B) is implicated in cell proliferation, but its role in tumorigenesis remains unclear. METHODS AND RESULTS: Immunohistochemical analysis of ARID1B expression using breast cancer tissue microarrays containing 156 breast invasive ductal carcinomapatient samples and subsequent statistical data analysis based on ARID1B immunoreactivity score were performed to examine the correlation between clinicopathological parameters in breast cancer and ARID1B expression. In-vitro assays were also performed to study the role of ARID1B in cell cycle progression. Univariate analysis revealed that high ARID1B expression is correlated closely with histological grade (P = 0.045) and size (P = 0.043) of invasive breast cancer. These findings were confirmed by multivariate analysis. Notably, increased ARID1B expression was frequently detected in the aggressive triple-negative breast cancer subtypes (P = 0.039) and associated with decreased 5-year disease-free survival rate. Lastly, MDA-MB-231 cells with reduced ARID1B activity displayed a delay in G1 to S phase cell cycle transition and consequently showed a decrease in cell proliferation compared with controls (P < 0.001). CONCLUSIONS:ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer.
Authors: L M Saleh; W Wang; S E M Herman; N S Saba; V Anastas; E Barber; M Corrigan-Cummins; M Farooqui; C Sun; S M Sarasua; Z Zhao; N K Abousamra; O Elbaz; H A Abdelghaffar; A Wiestner; K R Calvo Journal: Leukemia Date: 2016-06-24 Impact factor: 11.528