The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-08-29 DOI:10.1002/jev2.12499
Lin Cao, Yue Zhou, Shuai Lin, Chunyan Yang, Zixuan Guan, Xiaofan Li, Shujie Yang, Tong Gao, Jiazhen Zhao, Ning Fan, Yanan Song, Dongmin Li, Xiang Li, Zhuo Li, Feng Guan, Zengqi Tan
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Abstract

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC.

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通过基于壳聚糖磁珠的分离和 DIA 蛋白组分析研究 HBV-HCC 的囊泡蛋白质组特征轨迹
肝细胞癌(HCC)是一种常见的原发性肝癌,通常与慢性乙型肝炎病毒感染(CHB)和肝硬化(LC)有关,这突出表明了发现生物标记物以改善患者预后的迫切需要。利用细胞外小泡(sEV)进行液体活检的蛋白质组学技术为生物标志物的开发提供了新的途径。在这里,我们评估了各种分离 sEV 的方法,并确定壳聚糖(CS)是一种最佳方法。随后,我们采用优化的基于 CS 的磁珠(Mag-CS)从健康对照、CHB、LC 和 HBV-HCC 患者的血清样本中分离出 sEV。利用与数据无关的采集质谱与机器学习相结合的方法,我们发现了潜在的囊泡蛋白生物标志物特征(KNG1、F11、KLKB1、CAPNS1、CDH1、CPN2、NME2),这些特征能够将 HBV-HCC 与 CHB、LC 和非 HBV-HCC 区分开来。总之,我们的研究结果凸显了基于 Mag-CS 的 sEV 分离技术在鉴定 HBV-HCC 早期检测生物标记物方面的实用性。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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