Quantitative Proteomic Analysis of Plasma Exosomes to Identify the Candidate Biomarker of Imatinib Resistance in Chronic Myeloid Leukemia Patients

作者：Mei‐Yong Li, Zhao Cui, Lian Chen, Fangyi Yao, Fangmin Zhong, Ying Chen, Shuai Xu, Junyao Jiang, Yu‐Lin Yang, Qinghua Min, Lin Jin, Haibin Zhang, Jing Liu, Xiaozhong Wang, Bo Huang · 发表于：Frontiers in Oncology · 年份：2021 · DOI：10.3389/fonc.2021.779567 · 被引用次数：47 · 研究领域：Chronic Myeloid Leukemia Treatments、Extracellular vesicles in disease、Mast cells and histamine

BACKGROUND: Imatinib (IM), a tyrosine kinase inhibitor (TKI), has markedly improved the survival and life quality of chronic myeloid leukemia (CML) patients. However, the lack of specific biomarkers for IM resistance remains a serious clinical challenge. Recently, growing evidence has suggested that exosome-harbored proteins were involved in tumor drug resistance and could be novel biomarkers for the diagnosis and drug sensitivity prediction of cancer. Therefore, we aimed to investigate the proteomic profile of plasma exosomes derived from CML patients to identify ideal biomarkers for IM resistance. METHODS: We extracted exosomes from pooled plasma samples of 9 imatinib-resistant CML patients and 9 imatinib-sensitive CML patients by ultracentrifugation. Then, we identified the expression levels of exosomal proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based label free quantification. Bioinformatics analyses were used to analyze the proteomic data. Finally, the western blot (WB) and parallel reaction monitoring (PRM) analyses were applied to validate the candidate proteins. RESULTS: A total of 2812 proteins were identified in plasma exosomes from imatinib-resistant and imatinib-sensitive CML patients, including 279 differentially expressed proteins (DEPs) with restricted criteria (fold change≥1.5 or ≤0.667, p<0.05). Compared with imatinib-sensitive CML patients, 151 proteins were up-regulated and 128 proteins were down-regulated. Bioinformatics analyses...