Mao Guochao, Zheng Yi, Lin Shuai, Ma Li, Zhou Zhangjian, Zhang Shuqun
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710000, People's Republic of China.
Int J Gen Med. 2021 Dec 1;14:9181-9191. doi: 10.2147/IJGM.S343948. eCollection 2021.
Breast cancer (BC) has become the malignant tumor with the highest incidence worldwide. As a critical components of epigenetic regulation complexes, chromobox (CBX) family members inhibit the transcription of target genes through chromatin modification, leading to the progression of various human diseases and cancers. So far, little is known about the role of different CBX members in BC, especially their association with immune cells.
We conducted the analysis of differential expression of CBXs using Oncomine and GEPIA, prognostic value of CBXs using GEPIA and Kaplan-Meier, genetic interaction of CBXs using cBioPortal and GeneMANIA, and immune cell infiltration of CBXs in BC patients using TIMER.
The CBX2/3/4/8 expression levels were increased significantly, while the CBX6/7 expression levels were decreased. We found that CBX3 was significantly correlated with clinicopathological staging and short DFS in BC patients. High CBX3/5 expression was correlated with short OS in BC patients, while high expression of CBX4 was correlated with long OS in BC patients. In addition, the functions of CBXs family members mainly focus on methylated histone residue binding and chromatin organization. The CBXs expressions were closely related to the infiltration level of a variety of immune cells, including CD4/8+ T cells, B cells, neutrophils, macrophages and dendritic cells in BC cancers. The correlation between CBXs and immune cell infiltration was more common in Luminal BC than in Basal and Her-2 type.
This study may provide a new understanding for selection of molecular typing, therapeutic and prognostic biomarkers of CBX family in BC.
乳腺癌已成为全球发病率最高的恶性肿瘤。作为表观遗传调控复合物的关键组成部分,染色体框(CBX)家族成员通过染色质修饰抑制靶基因转录,导致各种人类疾病和癌症的进展。到目前为止,关于不同CBX成员在乳腺癌中的作用,尤其是它们与免疫细胞的关联,人们了解甚少。
我们使用Oncomine和GEPIA进行CBXs的差异表达分析,使用GEPIA和Kaplan-Meier进行CBXs的预后价值分析,使用cBioPortal和GeneMANIA进行CBXs的基因相互作用分析,并使用TIMER分析CBXs在乳腺癌患者中的免疫细胞浸润情况。
CBX2/3/4/8的表达水平显著升高,而CBX6/7的表达水平降低。我们发现CBX3与乳腺癌患者的临床病理分期和短无病生存期显著相关。CBX3/5高表达与乳腺癌患者短总生存期相关,而CBX4高表达与乳腺癌患者长总生存期相关。此外,CBX家族成员的功能主要集中在甲基化组蛋白残基结合和染色质组织。CBXs的表达与多种免疫细胞的浸润水平密切相关,包括乳腺癌中的CD4/8+T细胞、B细胞、中性粒细胞、巨噬细胞和树突状细胞。CBXs与免疫细胞浸润之间的相关性在Luminal型乳腺癌中比在基底型和Her-2型中更常见。
本研究可能为乳腺癌中CBX家族的分子分型、治疗和预后生物标志物的选择提供新的认识。