Liang Yuan-Ke, Lin Hao-Yu, Chen Chun-Fa, Zeng De
The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, China.
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Oncotarget. 2017 Sep 28;8(54):92375-92387. doi: 10.18632/oncotarget.21325. eCollection 2017 Nov 3.
Chromobox (CBX) family proteins are canonical components in polycomb repressive complexes 1 (PRC1), with epigenetic regulatory function and transcriptionally repressing target genes via chromatin modification. A plethora of studies have highlighted the function specifications among CBX family members in various cancer, including lung cancer, colon cancer and breast cancer. Nevertheless, the functions and prognostic roles of distinct CBX family members in breast cancer (BC) remain elusive. In this study, we reported the prognostic values of CBX family members in patients with BC through analysis of a series of databases, including , , Public Data Hubs, and Kaplan-Meier plotter. It was found that the mRNA expression of CBX family members were noticeably higher in BC than normal counterparts. CBX2 was highly expressed in Basal-like and HER-2 subtypes, while CBX4 and CBX7 expressions were enriched in Luminal A and Luminal B subtypes of BC. Survival analysis revealed that CBX1, CBX2 and CBX3 mRNA high expression was correlated to worsen relapse-free survival (RFS) for all BC patients, while CBX4, CBX5, CBX6 and CBX7 high expression was correlated to better RFS in this setting. Noteworthily, CBX1 and CBX2 were associated with chemoresistance whereas CBX7 was associated with tamoxifen sensitivity, as well as chemosensitivity in breast tumors. Therefore, we propose that CBX1, CBX2 and CBX7 are potential targets for BC treatment. The results might be beneficial for better understanding the complexity and heterogeneity in the molecular underpinning of BC, and to develop tools to more accurately predict the prognosis of patients with BC.
染色体盒（CBX）家族蛋白是多梳抑制复合物1（PRC1）的典型组成部分，具有表观遗传调控功能，并通过染色质修饰转录抑制靶基因。大量研究突出了CBX家族成员在包括肺癌、结肠癌和乳腺癌在内的各种癌症中的功能特异性。然而，不同CBX家族成员在乳腺癌（BC）中的功能和预后作用仍不清楚。在本研究中，我们通过分析一系列数据库，包括 、 、公共数据中心和Kaplan-Meier绘图仪，报告了CBX家族成员在BC患者中的预后价值。发现BC中CBX家族成员的mRNA表达明显高于正常对照。CBX2在基底样和HER-2亚型中高表达，而CBX4和CBX7的表达在BC的腔面A和腔面B亚型中富集。生存分析显示，CBX1、CBX2和CBX3 mRNA高表达与所有BC患者无复发生存期（RFS）恶化相关，而CBX4、CBX5、CBX6和CBX7高表达与该情况下更好的RFS相关。值得注意的是，CBX1和CBX2与化疗耐药相关，而CBX7与他莫昔芬敏感性以及乳腺肿瘤的化疗敏感性相关。因此，我们提出CBX1、CBX2和CBX7是BC治疗的潜在靶点。这些结果可能有助于更好地理解BC分子基础的复杂性和异质性，并开发工具以更准确地预测BC患者的预后。
