Li Xiaoxi, Zhang Chenxiao, Deng Minyao, Jiang Yong, He Zhengjin, Qian Hui
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
iScience. 2023 Dec 7;27(1):108667. doi: 10.1016/j.isci.2023.108667. eCollection 2024 Jan 19.
The multi-omics data has greatly improved the molecular diagnosis of B-cell neoplasms, but there is still a lack of predictive biomarkers to guide precision therapy. Here, we analyzed publicly available data and found that B-cell neoplasm cell lines with different levels of EFNB1 had distinctive drug response patterns of inhibitors targeting SRC/PI3K/AKT. Overexpression of EFNB1 promoted phosphorylation of key proteins in drug response, such as SRC and STMN1, conferring sensitivity to SRC inhibitor and cytotoxic drugs. EFNB1 phosphorylation signaling network was significantly associated with the prognosis of GCB-DLBCL patients. Moreover, EFNB1 levels were correlated with cell of origin (COO) scores, suggesting that EFNB1 is a quantitative indicator of cell differentiation. Ultimately, we proposed a model for the stratification of human B-cell malignancies and the implementation of targeted therapies based on EFNB1 levels. Our findings highlight that EFNB1 level is a promising biomarker for predicting drug response, COO and prognosis.
多组学数据极大地改善了B细胞肿瘤的分子诊断，但仍缺乏预测性生物标志物来指导精准治疗。在此，我们分析了公开可用的数据，发现具有不同水平EFNB1的B细胞肿瘤细胞系对靶向SRC/PI3K/AKT的抑制剂有独特的药物反应模式。EFNB1的过表达促进了药物反应中关键蛋白（如SRC和STMN1）的磷酸化，赋予了对SRC抑制剂和细胞毒性药物的敏感性。EFNB1磷酸化信号网络与GCB-DLBCL患者的预后显著相关。此外，EFNB1水平与起源细胞（COO）评分相关，表明EFNB1是细胞分化的定量指标。最终，我们提出了一种基于EFNB1水平对人类B细胞恶性肿瘤进行分层和实施靶向治疗的模型。我们的研究结果突出表明，EFNB1水平是预测药物反应、COO和预后的一个有前景的生物标志物。
