Yang An-Ping, Liu Leyna G, Chen Min-Min, Liu Fang, You Hua, Liu Lian, Yang Hua, Xun Yang, Liu Jing, Wang Rui-Xue, Brand David D, Liu Dahai, Zheng Song Guo, Li Wen-Xing
School of Stomatology and Medicine, Foshan University Foshan 528000, Guangdong, China.
Portola High School 1001 Cadence, Irvine 92618, CA, USA.
Am J Transl Res. 2019 Jul 15;11(7):4382-4396. eCollection 2019.
Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our results showed that signaling pathways, amino acid metabolism and several lipid metabolism pathways varies considerably among these three types of lymphoma. Furthermore, we identified several key transcription factors (TFs) and their target genes that may promote these diseases by influencing multiple carcinogenic pathways. Among these TFs, we reported first that E2F8 displayed the most significant effects in BURK and MCL. Our results demonstrate that over-expression of E2F8 activates target genes that may promote cell cycle, mitosis, immune and other cancer related functions in BURK and MCL. Therefore, we suggest that E2F8 could be used as a biomarker and potential therapeutic target for BURK and MCL. These findings would be helpful in the study of pathogenesis, and drug discovery and also in the prognosis of B cell lymphomas.
伯基特淋巴瘤（BURK）、弥漫性大B细胞淋巴瘤（DLBCL）和套细胞淋巴瘤（MCL）是B细胞淋巴瘤的三种主要类型。本研究旨在比较受影响的生物学功能和通路的差异，以及探索BURK、DLBCL和MCL中可能的调控机制和潜在治疗靶点。我们对10个淋巴瘤数据集进行了综合分析，包括352例BURK患者、880例DLBCL患者、216例MCL患者和33例对照。我们的结果表明，这三种类型的淋巴瘤在信号通路、氨基酸代谢和几种脂质代谢通路上存在显著差异。此外，我们鉴定了几种关键转录因子（TFs）及其靶基因，它们可能通过影响多种致癌途径促进这些疾病。在这些TFs中，我们首次报道E2F8在BURK和MCL中表现出最显著的作用。我们的结果表明，E2F8的过表达激活了可能促进BURK和MCL中细胞周期、有丝分裂、免疫和其他癌症相关功能的靶基因。因此，我们建议E2F8可作为BURK和MCL的生物标志物和潜在治疗靶点。这些发现将有助于B细胞淋巴瘤的发病机制研究、药物发现以及预后判断。
