小细胞外囊泡在乳腺癌诊断与治疗中的研究进展<sup>*</sup>

doi:10.13523/j.cb.2308041

中国生物工程杂志

2024, Vol. 44

Issue (4): 54-66 DOI: 10.13523/j.cb.2308041

综述

小细胞外囊泡在乳腺癌诊断与治疗中的研究进展^*

王尚志¹,章瑾¹,杨明睿¹,闫滨^2,^**(

)

1 山东中医药大学药学院济南 250355
2 山东中医药大学中医学院济南 250355

Research Progress of Small Extracellular Vesicles in the Diagnosis and Treatment of Breast Cancer

WANG Shangzhi¹,ZHANG Jin¹,YANG Mingrui¹,YAN Bin^2,^**(

)

1 School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
2 College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China

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摘要：

小细胞外囊泡(small extracellular vesicles,sEVs)是一类具有脂质双层膜结构的细胞外囊泡,能够参与细胞间通讯,是一种良好的药物递送载体。小细胞外囊泡中的微小RNA(miRNA)、长链非编码RNA(long non-coding RNA,lncRNA)、环状RNA(circRNA)和蛋白质等多种成分参与调控肿瘤发生发展的重要机制,能够反映细胞的生理状态与功能状态,且大量存在于患者的血浆、尿液、唾液中,对小细胞外囊泡进行分析和检测可能成为肿瘤诊断的新型手段。除了作为肿瘤诊断的生物标志物,小细胞外囊泡还通过其内容物或作为特异性药物递送载体来调控肿瘤细胞的侵袭转移、机体耐药、细胞因子分泌表达与免疫应答,发挥其抗肿瘤作用。总结近五年来小细胞外囊泡中RNA(miRNA、lncRNA、circRNA)与蛋白质作为乳腺癌诊断的生物标志物以及在乳腺癌治疗中的潜力的相关研究,阐述小细胞外囊泡作为新型诊断与治疗方法的优势与不足,为小细胞外囊泡在乳腺癌诊疗领域的临床应用提供参考。

关键词： 小细胞外囊泡; 外泌体; 乳腺癌; 生物标志物; 递送载体; 诊疗

Abstract:

Small extracellular vesicles (sEVs) are a class of extracellular vesicles with a lipid bilayer membrane structure, which can participate in intercellular communication and be used as nanovesicles for drug delivery. The microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and proteins in sEVs are important mechanisms to regulate the development of tumors, and reflect the physiological and functional states of cells. They are present in large quantities in the plasma, urine, and saliva of patients, so the analysis and detection of sEVs may become a novel means of tumor diagnosis. In addition to being a biomarker for tumor diagnosis, sEVs can also regulate the invasion and metastasis of tumor cells, drug resistance, cytokine secretion and expression, and immune response via their contents or as specific drug delivery carriers to exert their anti-tumor effects. This paper summarizes the last five years of research on the use of RNAs (miRNAs, lncRNAs, circRNAs) and proteins in sEVs as biomarkers for breast cancer diagnosis and their therapeutic potential in breast cancer, and describes the advantages and shortcomings of sEVs as a new type of diagnostic and therapeutic method to provide references for the future clinical application of sEVs in the field of breast cancer diagnosis and treatment.

Key words: Small extracellular vesicles Exosomes Breast cancer Biomarkers Delivery carrier Diagnosis and treatment

收稿日期: 2023-08-31 出版日期: 2024-04-30

ZTFLH:

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基金资助: * 国家卫生部重大新药创制科技重大专项(2014ZX09509001001)

通讯作者: ** 电子信箱:60020078@sdutcm.edu.cn

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引用本文:

王尚志, 章瑾, 杨明睿, 闫滨. 小细胞外囊泡在乳腺癌诊断与治疗中的研究进展^*[J]. 中国生物工程杂志, 2024, 44(4): 54-66.

WANG Shangzhi, ZHANG Jin, YANG Mingrui, YAN Bin. Research Progress of Small Extracellular Vesicles in the Diagnosis and Treatment of Breast Cancer. China Biotechnology, 2024, 44(4): 54-66.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2308041 或 https://manu60.magtech.com.cn/biotech/CN/Y2024/V44/I4/54

图1 小细胞外囊泡的分子结构

图2 小细胞外囊泡的合成、分泌、摄取

表1 常用小细胞外囊泡分离方法优缺点比较

表2 常用乳腺癌诊断方法优缺点比较

小细胞外囊泡货物	表达变化	外泌体来源	样本数量	诊断效果	参考文献
miR-18a-3p	上调	血清	12名乳腺癌患者和12名乳腺纤维瘤患者	AUC = 0.83	[29]
miR-1246	上调	血浆	33名乳腺癌患者和37名健康对照者	灵敏度93.94% 特异度97.30%	[30]
miR-148a	下调	血清	125名乳腺癌患者和50名良性乳腺肿瘤患者	灵敏度84.0% 特异度80.0%	[31]
miR-7641	上调	血浆	13名远处转移乳腺癌患者和15名无远处转移乳腺癌患者	-	[18]
miR-1246、miR-206、miR-24和miR-373	下调	血浆	226名乳腺癌患者和146名健康对照者	灵敏度98.0% 特异度96.0%	[32]
miR-424、miR-423、miR-660和let7-Ⅰ	上调、下调	尿液	69名乳腺癌患者和40名健康对照者	灵敏度98.6% 特异度100%	[33]
XIST	上调	血清	91名TNBC术后患者	灵敏度84.2% 特异度92.3%	[34]
H19	上调	血清	50名乳腺癌患者、50名良性乳腺肿瘤患者和50名健康对照者	灵敏度87.0% 特异度70.6%	[35]
HOTAIR	上调	血浆	23名乳腺癌患者	-	[36]
HOTAIR	上调	血清	15名手术治疗的乳腺癌患者和 15名健康对照者	AUC=0.917 8	[37]
hsa_circ_0005552、hsa_circ_0007177、 hsa_circ_0002190、hsa_circ_0001439、 hsa_circ_0000642、hsa_circ_0006404、 hsa_circ_0000267、hsa_circ_0001073和 hsa_circ_0001417	上调	血浆	144名乳腺癌患者、72名良性乳腺肿瘤患者和43名健康对照者	AUC=0.80	[39]
has_circ_0009634、hsa_circ_0020707、 hsa_circ_0064923、hsa_circ_0104852 和hsa_circ_0087064	上调	血清	3名局限性乳腺癌患者、3名转移性乳腺癌患者和3名匹配的健康对照者	-	[40]
cirHIF1A	上调	血浆	24名乳腺癌患者和68名健康对照者	AUC=0.897	[41]
circKDM4C	下调	组织	乳腺癌患者肿瘤组织和正常组织	-	[42]
exo-AnxA2	上调	血清	169名乳腺癌患者和68名健康对照者	AUC=1.000	[43]
Del-1	上调	血浆	22名乳腺癌患者	-	[44]
miR-150-5p miR-576-3p miR -4665-5p	上调	血浆	27名乳腺癌患者和3名健康对照者	AUC=0.705 AUC=0.691 AUC=0.681	[51]
miR-188-3p、miR-501-3p、miR-502-3p、 miR-532-3p和miR-532-5p	上调	血清	204名乳腺癌患者和202名健康对照者	AUC=0.821~0.969	[52]
miR-188-3p、miR-500a-5p和miR-501-5p	上调	血浆	200名乳腺癌患者和190名健康对照者	AUC=0.805	[52]
miR-363-5p	下调	血浆	10名乳腺癌患者和10名健康对照者	AUC = 0.733~0.958	[53]
let-7b-5p、miR-106a-5p、miR-19a-3p、 miR-19b-3p、miR-25-3p、miR-425-5p、 miR-451a、miR-92a-3p、miR-93-5p、 miR-16-5p	上调	血清	216名乳腺癌患者和214名健康对照者	灵敏度91.6% 特异度91.3%	[54]

表3 小细胞外囊泡在乳腺癌中的诊断作用

表4 常用乳腺癌治疗方法优缺点比较

图3 小细胞外囊泡在乳腺癌治疗中的潜力

表5 小细胞外囊泡在乳腺癌中的治疗作用

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