Shao Fei, Guo Tiantian, Chua Pei Jou, Tang Lili, Thike Aye Aye, Tan Puay-Hoon, Bay Boon Huat, Baeg Gyeong Hun
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Histopathology. 2015 Nov;67(5):709-18. doi: 10.1111/his.12701. Epub 2015 May 17.
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.
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).
ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer.
鉴定乳腺癌的预后和预测生物标志物对于更好地对患者进行治疗分层和评估患者预后至关重要。富含AT的互作结构域蛋白1B（ARID1B）与细胞增殖有关，但其在肿瘤发生中的作用仍不清楚。
使用包含156例乳腺浸润性导管癌患者样本的乳腺癌组织芯片对ARID1B表达进行免疫组织化学分析，并基于ARID1B免疫反应评分进行后续统计数据分析，以研究乳腺癌临床病理参数与ARID1B表达之间的相关性。还进行了体外试验以研究ARID1B在细胞周期进程中的作用。单因素分析显示，ARID1B高表达与浸润性乳腺癌的组织学分级（P = 0.045）和大小（P = 0.043）密切相关。多因素分析证实了这些发现。值得注意的是，在侵袭性三阴性乳腺癌亚型中经常检测到ARID1B表达增加（P = 0.039），并且与5年无病生存率降低相关。最后，与对照组相比，ARID1B活性降低的MDA-MB-231细胞在G1期到S期的细胞周期转换中出现延迟，因此细胞增殖减少（P < 0.001）。
ARID1B可能作为一种有价值的预后和预测生物标志物以及乳腺癌的治疗靶点。
