Institute of Hematology, Provincial Key Laboratory of Biotechnology, School of Medicine, Northwest University, Xi'an, Shaanxi, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
J Extracell Vesicles. 2024 Sep;13(9):e12499. doi: 10.1002/jev2.12499.
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.
肝细胞癌 (HCC) 是一种常见的原发性肝癌，常与慢性乙型肝炎病毒感染 (CHB) 和肝硬化 (LC) 相关，这凸显了发现生物标志物以改善患者预后的重要性。蛋白质组学技术利用来自小细胞外囊泡 (sEV) 的液体活检，作为生物标志物开发的有前途的途径，提供了新的见解。在这里，我们评估了几种 sEV 分离方法，并确定多糖壳聚糖 (CS) 是一种最佳方法。随后，我们从健康对照者、CHB、LC 和 HBV-HCC 患者的血清样本中，使用优化的基于 CS 的磁性珠 (Mag-CS) 进行 sEV 分离。利用数据非依赖性采集质谱联用机器学习，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)，能够区分 HBV-HCC 与 CHB、LC 和非 HCC 情况。总的来说，我们的研究结果突出了基于 Mag-CS 的 sEV 分离在鉴定 HBV-HCC 早期检测生物标志物方面的应用。
