Department of Pediatrics, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, PR China.
Department of Embryo Laboratory, Changsha Reproductive Medical Hospital, Changsha, Hunan 410000, PR China.
Gene. 2022 Mar 1;813:146092. doi: 10.1016/j.gene.2021.146092. Epub 2021 Dec 9.
Diffuse large B-cell lymphoma (DLBCL) is the main pathological type of non-Hodgkin lymphoma (NHL). Chromobox (CBX) family proteins are classical components of polycomb group (PcG) complexes in many cancer types, resulting in accelerated carcinogenesis. Nevertheless, the prognostic, functional and expression significance of these CBX family members in DLBCL remain unclear and elusive.
CBX transcriptional levels were confirmed using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) databases. The protein levels of CBX family members were analysed using The Human Protein Atlas (HPA) database. Information on the PPI network, functional enrichment, drug sensitivity, prognostic value, miRNA network, protein structure, genetic alteration and immune cell infiltration were generated using the GeneMANIA, Metascape, GSCALite, GEPIA, PDB, cBioPortal, and TIMER databases, and the correlation of these factors with CBX expression levels in DLBCL was assessed.
CBX1/2/3/5/6/8 mRNA levels were significantly enhanced in DLBCL tissues compared to corresponding normal tissues. CBX1/3/4/5/8 protein expression levels were obviously increased, whereas CBX7 was obviously decreased. This difference might be attributed to miRNA regulation based on the miRNA network. Overall survival (OS) analysis showed that CBX levels were not correlated with prognosis in DLBCL patients, indicating that CBXs are not good biomarkers for DLBCL patients. Furthermore, functional enrichment analyses indicated that CBXs were closely related to DNA duplex unwinding, covalent chromatin modification, and histone lysine methylation. The levels of CBXs were also significantly associated with diverse immune cell infiltration in DLBCL.
This study reveals that dysregulated CBXs are involved in DLBCL development and might represent potential therapeutic targets for DLBCL.
弥漫性大 B 细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤(NHL)的主要病理类型。染色质盒(CBX)家族蛋白是许多癌症类型中多梳组(PcG)复合物的经典组成部分,导致致癌作用加速。然而,这些 CBX 家族成员在 DLBCL 中的预后、功能和表达意义仍不清楚。
使用 Oncomine、基因表达谱交互式分析(GEPIA)和癌症细胞系百科全书(CCLE)数据库证实 CBX 转录水平。使用人类蛋白质图谱(HPA)数据库分析 CBX 家族成员的蛋白水平。使用 GeneMANIA、Metascape、GSCALite、GEPIA、PDB、cBioPortal 和 TIMER 数据库生成 PPI 网络、功能富集、药物敏感性、预后价值、miRNA 网络、蛋白质结构、遗传改变和免疫细胞浸润的信息,并评估这些因素与 CBX 在 DLBCL 中的表达水平的相关性。
与相应的正常组织相比,DLBCL 组织中 CBX1/2/3/5/6/8 mRNA 水平显著升高。CBX1/3/4/5/8 蛋白表达水平明显升高,而 CBX7 蛋白表达水平明显降低。这种差异可能归因于 miRNA 网络的调节。总体生存(OS)分析表明,CBX 水平与 DLBCL 患者的预后无关,表明 CBX 不是 DLBCL 患者的良好生物标志物。此外,功能富集分析表明,CBX 与 DNA 双链解旋、共价染色质修饰和组蛋白赖氨酸甲基化密切相关。CBX 水平也与 DLBCL 中不同免疫细胞浸润显著相关。
本研究表明,失调的 CBX 参与 DLBCL 的发生发展,可能成为 DLBCL 的潜在治疗靶点。