EFNB1 levels determine distinct drug response patterns guiding precision therapy for B-cell neoplasms

Xiaoxi Li; Chenxiao Zhang; Minyao Deng; Yong Jiang; Zhengjin He; Hui Qian

doi:10.1016/j.isci.2023.108667

EFNB1 levels determine distinct drug response patterns guiding precision therapy for B-cell neoplasms

iScience. 2023 Dec 7;27(1):108667. doi: 10.1016/j.isci.2023.108667. eCollection 2024 Jan 19.

Authors

Xiaoxi Li¹, Chenxiao Zhang¹, Minyao Deng¹, Yong Jiang¹, Zhengjin He², Hui Qian¹

Affiliations

¹ Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
² 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.

Abstract

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.

Keywords: Cancer; Molecular biology; Omics.