Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
Department of Respiratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
Clin Breast Cancer. 2023 Jun;23(4):e206-e218. doi: 10.1016/j.clbc.2023.02.007. Epub 2023 Feb 15.
Chromobox proteins are canonical components of the Polycomb group family and play pivotal roles in several cancers. However, little is known about the function, prognostic value and drug sensitivity of CBX family members in breast cancer.
In this study we investigated the expression, prognosis value and drug sensitivity of CBX family in breast cancer using the ONCOMINE, GEPIA, Human Protein Atlas and Kaplan-Meier Plotter databases, etc. and preliminary verified the expression of CBX family in breast cancer cell lines by RT-qPCR.
We found that the expression levels of CBX1/2/3/4/8 members were elevated in breast cancer tissues compared to adjacent normal breast tissues, while the expression levels of CBX6/7 genes were reduced in breast cancer tissue. In vitro qRT-PCR validated the expression differences of CBX1/2/3/4/8 in breast cancer cell lines. Further analysis showed expression of CBX family members was remarkably correlated with cancer subgroups. As nodal metastasis status increased, the mRNA expression of CBX1/2/3/4/8 members tended to be higher, while CBX6/7 tended to be lower. The expression of CBX1/2/3 was higher in patients with TP53 mutation and CBX6/7 expression tended to be lower in patients with TP53 mutation groups. High transcription levels of CBX2/3 were significantly associated with shorter overall survival in breast cancer patients, while lower expression of CBX4/5/6/7 members was associated with unfavorable overall survival. Moreover, a high mutation rate of CBX gene members (43%) was observed in breast cancer patients, and genetic alterations in CBX genes was associated with poor prognosis.
Taken together, our results indicated that CBX2/3/6/7/8 could be considered prognostic and therapeutic biomarkers of breast cancer and are worthy of further study.
染色盒蛋白是多梳组家族的典型组成部分，在几种癌症中发挥关键作用。然而，关于 CBX 家族成员在乳腺癌中的功能、预后价值和药物敏感性知之甚少。
本研究通过 ONCOMINE、GEPIA、Human Protein Atlas 和 Kaplan-Meier Plotter 数据库等，研究了 CBX 家族在乳腺癌中的表达、预后价值和药物敏感性，并通过 RT-qPCR 初步验证了 CBX 家族在乳腺癌细胞系中的表达。
我们发现 CBX1/2/3/4/8 成员在乳腺癌组织中的表达水平高于相邻正常乳腺组织，而 CBX6/7 基因在乳腺癌组织中的表达水平降低。体外 qRT-PCR 验证了 CBX1/2/3/4/8 在乳腺癌细胞系中的表达差异。进一步分析表明，CBX 家族成员的表达与癌症亚组显著相关。随着淋巴结转移状态的增加，CBX1/2/3/4/8 成员的 mRNA 表达趋于升高，而 CBX6/7 则趋于降低。TP53 突变患者的 CBX1/2/3 表达较高，而 TP53 突变患者的 CBX6/7 表达倾向于降低。CBX2/3 的高转录水平与乳腺癌患者的总生存期较短显著相关，而 CBX4/5/6/7 成员的低表达与总生存期不良相关。此外，在乳腺癌患者中观察到 CBX 基因成员的高突变率（43%），CBX 基因的遗传改变与预后不良相关。
综上所述，我们的研究结果表明 CBX2/3/6/7/8 可作为乳腺癌的预后和治疗标志物，值得进一步研究。
