检验医学 ›› 2026, Vol. 41 ›› Issue (9): 922-928.DOI: 10.3969/j.issn.1673-8640.2026.09.017
收稿日期:2024-08-28
修回日期:2025-06-06
出版日期:2026-09-30
发布日期:2026-09-29
通讯作者:
丁海涛,E-mail:作者简介:李学敏,女,2001年生,硕士,主要从事乳腺癌外泌体早期诊断研究。
LI Xuemin, LI Xiaocong, DING Haitao(
)
Received:2024-08-28
Revised:2025-06-06
Online:2026-09-30
Published:2026-09-29
摘要:
乳腺癌的早期诊断是改善患者预后的关键,现有临床诊断方法存在创伤性较高或敏感性不足等局限。外泌体作为肿瘤细胞分泌的纳米级囊泡,因具有非侵入性获取、体液中丰度高且携带特异性生物分子等优势,已成为乳腺癌液体活检领域的新型生物标志物。文章系统综述外泌体在乳腺癌早期诊断中的研究进展,重点阐述其作为诊断标志物的生物学基础,详细归纳核酸类和膜蛋白类标志物的最新研究成果,并比较各类外泌体分离检测技术的优缺点和应用场景。尽管外泌体展现出巨大的临床应用潜力,但其临床转化仍面临分离标准化、异质性干扰和检测成本较高等挑战。未来,通过多组学整合分析与新型检测技术的开发,有望推动外泌体在乳腺癌早期精准诊断中实现突破。
中图分类号:
李学敏, 李晓聪, 丁海涛. 外泌体在乳腺癌早期诊断中的研究进展[J]. 检验医学, 2026, 41(9): 922-928.
LI Xuemin, LI Xiaocong, DING Haitao. Research progress of exosomes in the early diagnosis of breast cancer[J]. Laboratory Medicine, 2026, 41(9): 922-928.
| 分离方法 | 优点 | 缺点 | 应用场景 |
|---|---|---|---|
| 超速离心法 | 操作标准化,可重复性强,被视为金标准;避免化学试剂污染,适合后续功能研究;适应不同样本体积,适用于大规模生产[ | 纯度低;多次离心步骤易导致外泌体破裂或损失,回收率低;对高黏度或杂质多的生物流体(如血浆)效果差,需预处理[ | 细胞培养基或大型体液样本;大规模外泌体生产;后续机制研究[ |
| 免疫亲和法 | 高选择性分离,减少非外泌体颗粒污染;适用于复杂生物流体(如血液),提高特异性富集;可用于检测癌症标志物,提升诊断敏感性 | 成本较高,需要特定抗体或亲和材料;某些样本类型(如富含杂质的体液)效率不稳定 | 基于特定表面标记物的高纯度外泌体分离,如用于疾病诊断或生物标志物研究[ |
| 超滤法 | 操作快速,适合大样本体积 处理 | 可能导致外泌体破裂或结构损伤;杂质残留风险高,纯度 较低 | 基于尺寸差异的快速预处理或检测步骤,尤其适用于简化样本过滤过程[ |
| 尺寸排阻色谱 | 高纯度分离,保留外泌体结构完整性 | 对小体积样本回收率不高 | 提供高纯度分离的首选方法,特别适用于临床样本分析,以减少污染物干扰[ |
| 聚合物共沉淀法 | 操作简单,成本低;回收率较高 | 纯度低,可能残留聚合物杂质 | 常规批量应用(如药物递送研究)[ |
| 微流控技术 | 快速、便携,整合度高,减少损失;高纯度、高产量,适用于临床诊断 | 技术相对新,设备成本可能高 | 特别适用于高吞吐量分离和分析,如便携式设备开发[ |
表1 外泌体分离方法的优缺点和适用场景
| 分离方法 | 优点 | 缺点 | 应用场景 |
|---|---|---|---|
| 超速离心法 | 操作标准化,可重复性强,被视为金标准;避免化学试剂污染,适合后续功能研究;适应不同样本体积,适用于大规模生产[ | 纯度低;多次离心步骤易导致外泌体破裂或损失,回收率低;对高黏度或杂质多的生物流体(如血浆)效果差,需预处理[ | 细胞培养基或大型体液样本;大规模外泌体生产;后续机制研究[ |
| 免疫亲和法 | 高选择性分离,减少非外泌体颗粒污染;适用于复杂生物流体(如血液),提高特异性富集;可用于检测癌症标志物,提升诊断敏感性 | 成本较高,需要特定抗体或亲和材料;某些样本类型(如富含杂质的体液)效率不稳定 | 基于特定表面标记物的高纯度外泌体分离,如用于疾病诊断或生物标志物研究[ |
| 超滤法 | 操作快速,适合大样本体积 处理 | 可能导致外泌体破裂或结构损伤;杂质残留风险高,纯度 较低 | 基于尺寸差异的快速预处理或检测步骤,尤其适用于简化样本过滤过程[ |
| 尺寸排阻色谱 | 高纯度分离,保留外泌体结构完整性 | 对小体积样本回收率不高 | 提供高纯度分离的首选方法,特别适用于临床样本分析,以减少污染物干扰[ |
| 聚合物共沉淀法 | 操作简单,成本低;回收率较高 | 纯度低,可能残留聚合物杂质 | 常规批量应用(如药物递送研究)[ |
| 微流控技术 | 快速、便携,整合度高,减少损失;高纯度、高产量,适用于临床诊断 | 技术相对新,设备成本可能高 | 特别适用于高吞吐量分离和分析,如便携式设备开发[ |
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