外泌体在生物标志物研究领域的文献计量学分析

doi:10.3724/SP.J.1123.2025.01025

摘要/Abstract

摘要：

外泌体是细胞分泌的细胞外囊泡的一种亚型,携带丰富的遗传物质及蛋白质等,外泌体膜表面有众多母细胞特有的标志物,已成为疾病诊断、疾病进展以及疾病治疗的重要依据。本文在Web of Science core collection(SCI-EXPENED)数据库中,检索2010-2024年间研究主题为“外泌体”与“生物标志物”或“诊断”或“液体活检”的研究型和综述类论文。文献计量分析结果显示,外泌体作为生物标志物标记疾病的研究关注度逐渐升高,中国是该研究的主要贡献国家;文献主要围绕癌症、炎症、糖尿病、神经退行性疾病和心血管疾病的标记诊断展开研究;通常使用色谱、质谱、拉曼光谱等技术分析外泌体核酸、蛋白质、代谢物等;常用的检验样本为血浆、血清、尿液、唾液、脑脊液等体液;外泌体作为肿瘤标志物的研究主要聚焦于肺癌、乳腺癌、前列腺癌等8种具有高发病率的癌症。本文聚焦于外泌体作为疾病生物标志物的研究领域,利用文献计量工具系统分析了2010-2024年间外泌体及其内容物作为生物标志物在疾病诊断领域中的应用,并对外泌体介导的疾病诊断和疾病治疗的发展前景和未来努力方向进行了分析和展望,期望为外泌体在疾病标志及应用方面的研究提供参考。

关键词: 外泌体, 生物标志物, 液体活检, 疾病诊断, 文献计量学分析

Abstract:

Exosomes are extracellular vesicles secreted by cells and are rich in genetic material and proteins. The surfaces of exosome membranes contain many blast-specific markers that provide an important basis for disease diagnosis, progression, and treatment. Herein, we searched the Web of Science core collection (SCI-EXPENED) database for research and review articles on “exosomes” and “biomarkers” or “diagnostics” or “liquid biopsy” as research topics between 2010 and 2024. Bibliometric analysis revealed that exosomes have received increasing levels of attention as disease biomarkers, with China contributing the most to these studies. Herein, we focus on marker diagnoses for cancer, inflammation, and diabetes, as well as neurodegenerative and cardiovascular diseases. Chromatography, mass spectrometry, Raman spectroscopy, and other techniques are typically used to analyze exosomal nucleic acids, proteins, and metabolites, with commonly used test samples including plasma, serum, urine, saliva, cerebrospinal fluid, and other bodily fluids. Research into exosomes as tumor markers has mainly focused on eight highly prevalent cancers, including lung, breast, and prostate cancers. This paper focuses on exosomes as disease biomarkers and uses a bibliometric tool system to analyze the use of exosomes and their contents as biomarkers in the disease diagnosis field between 2010 and 2024, analyzes development prospects, and discusses future exosome-mediated efforts for diagnosing and treating diseases, and is expected to provide a reference for studying and applying exosomes as disease markers.

Key words: exosomes, biomarkers, liquid biopsy, disease diagnosis, bibliometric analysis

中图分类号:

O658

黄雨霞, 王海燕, 张屹涵, 蔺奕菲, 乔晓强, 胡良海. 外泌体在生物标志物研究领域的文献计量学分析[J]. 色谱, 2025, 43(5): 498-507.

HUANG Yuxia, WANG Haiyan, ZHANG Yihan, LIN Yifei, QIAO Xiaoqiang, HU Lianghai. Bibliometric analysis of exosomes in the biomarker research field[J]. Chinese Journal of Chromatography, 2025, 43(5): 498-507.

图/表 7

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Country	Post volume	Percentage/ %	Average cited	Institution	Post volume	Percentage/ %	Average cited
China	6084	37.3	32	Shanghai Jiao Tong University	339	2.0	37
United States	3987	24.5	57	Nanjing Medical University	302	1.8	44
Italy	1320	8.1	38	Fudan University	290	1.7	33
Germany	969	5.9	46	Chinese Academy of Sciences	229	1.4	38
Spain	737	4.5	46	Harvard Medical School	229	1.4	64
Japan	733	4.5	41	Zhejiang University	208	1.2	39
England	703	4.3	48	Central South University	207	1.2	24
Korea	627	3.8	38	Southern Medical University	192	1.2	36
Australia	577	3.5	57	Shandong University	191	1.1	39
India	565	3.5	21	Capital Medical University	187	1.1	29

Country	Post volume	Percentage/ %	Average cited	Institution	Post volume	Percentage/ %	Average cited
China	6084	37.3	32	Shanghai Jiao Tong University	339	2.0	37
United States	3987	24.5	57	Nanjing Medical University	302	1.8	44
Italy	1320	8.1	38	Fudan University	290	1.7	33
Germany	969	5.9	46	Chinese Academy of Sciences	229	1.4	38
Spain	737	4.5	46	Harvard Medical School	229	1.4	64
Japan	733	4.5	41	Zhejiang University	208	1.2	39
England	703	4.3	48	Central South University	207	1.2	24
Korea	627	3.8	38	Southern Medical University	192	1.2	36
Australia	577	3.5	57	Shandong University	191	1.1	39
India	565	3.5	21	Capital Medical University	187	1.1	29

Cluster	Keywords^*
#0 colorectal cancer	miR-21; signaling pathway; metabolism; mesenchymal stem cell; long non-coding RNA therapeutic target; tumor associated macrophages; macrophage polarization; phenotype; outer membrane vesicles; non-coding RNAs; tumor suppressor; fibroblasts; noncoding RNA; chemoresistance; cisplatin resistance; NF kappa-B; promote; microRNA expression; diagnostic biomarker; RNAs; autophagy; squamous cell carcinoma; poor prognosis; macrophages; prognostic biomarker; long noncoding RNAs; mesenchymal transition; tumor-microenvironment; circular RNAs; up regulation; roles; potential biomarkers; inhibition; long noncoding RNA; cancer cells; noncoding RNAs; epithelial mesenchymal transition; pathway; drug resistance; carcinoma; cell proliferation; down regulation; promotes; migration; circular RNA; gastric cancer; apoptosis; tumor microenvironment; angiogenesis; resistance; invasion; growth; hepatocellular carcinoma; progression; colorectal cancer; proliferation; metastasis
#1 liquid biopsy	promote tumor growth; cell derived microparticles; human saliva; smooth muscle cells; rheumatoid arthritis; pregnancy; mesenchymal stromal cells; cancer therapy; serum exosome; endothelial microparticles; horizontal transfer; multivesicular body; urinary exosome; progenitor cells; responses; cancer exosome; tissue; heart failure; tissue factor; intercellular transfer; adipose tissue; tumor growth; emerging role; size; insulin resistance; nanoparticle tracking analysis; myocardial infarction; circulating microparticles; cardiovascular disease; differentiation; pathogenesis; intercellular communication; in vivo; messenger RNAs; flow cytometry; mediated transfer; stromal cells; nanoparticles; T cells; transferrin receptor; tumor derived exosome; endothelial cells; drug delivery; membrane vesicles; delivery; dendritic cells; proteomic analysis; gene expression; inflammation; microparticles; cell derived exosome; in vitro; stem cells; mesenchymal stem cells; extracellular vesicles
#2 exosome	aptasensor; amplification; heterogeneity; KRAS; exosomal miRNA; chip; women; cell-free DNA; biopsy; tumor cells; mortality; target; nucleic acids; precision medicine; clinical significance; recurrence; DNA methylation; cell lung cancer system; chemotherapy; early diagnosis; mutations; bladder cancer; cancer diagnosis; marker; potential biomarker; cell free DNA; separation; free DNA; classification; management; prognosis; circulating tumor DNA; quantification; peripheral blood; circulating exosome; diagnostic biomarkers; gene; ovarian cancer; risk; survival; blood; pancreatic cancer; messenger RNA; DNA; lung cancer; circulating tumor cells; prostate cancer; breast cancer; liquid biopsy
#3 extracellular vesicles	progress; glioblastoma; diabetic nephropathy; head; discovery; platform; proteomics; genes; reveals; fibrosis; injury; miRNA; extracellular vesicles (EVs); receptor; exosome isolation; biology; communication; mass spectrometry; miRNAs; release; therapy; markers; mechanisms; mechanism; vesicles; activation; disease; secretion; microRNA; RNA; extracellular vesicle; circulating microRNAs; proteins; protein; serum; biomarker; plasma; biogenesis; diagnosis; identification; microRNAs; cancer; microvesicles; cells; biomarkers; expression; exosome
#4 Alzheimer’s disease	cognitive impairment; neuronal exosome; Tau; children; infection; dementia; blood brain barrier; multiple sclerosis; binding; dysfunction; amyloid beta; central nervous system; model; cell; small extracellular vesicles; alpha synuclein; association; Parkinson’s disease; brain; oxidative stress; cerebrospinal fluid; Alzheimer’s disease
#5 plasma diagnostics-interferometry	deposition; density; spectroscopy and imaging; plasma diagnostics-interferometry; temperature; plasma diagnostics; diagnostics

Cluster	Keywords^*
#0 colorectal cancer	miR-21; signaling pathway; metabolism; mesenchymal stem cell; long non-coding RNA therapeutic target; tumor associated macrophages; macrophage polarization; phenotype; outer membrane vesicles; non-coding RNAs; tumor suppressor; fibroblasts; noncoding RNA; chemoresistance; cisplatin resistance; NF kappa-B; promote; microRNA expression; diagnostic biomarker; RNAs; autophagy; squamous cell carcinoma; poor prognosis; macrophages; prognostic biomarker; long noncoding RNAs; mesenchymal transition; tumor-microenvironment; circular RNAs; up regulation; roles; potential biomarkers; inhibition; long noncoding RNA; cancer cells; noncoding RNAs; epithelial mesenchymal transition; pathway; drug resistance; carcinoma; cell proliferation; down regulation; promotes; migration; circular RNA; gastric cancer; apoptosis; tumor microenvironment; angiogenesis; resistance; invasion; growth; hepatocellular carcinoma; progression; colorectal cancer; proliferation; metastasis
#1 liquid biopsy	promote tumor growth; cell derived microparticles; human saliva; smooth muscle cells; rheumatoid arthritis; pregnancy; mesenchymal stromal cells; cancer therapy; serum exosome; endothelial microparticles; horizontal transfer; multivesicular body; urinary exosome; progenitor cells; responses; cancer exosome; tissue; heart failure; tissue factor; intercellular transfer; adipose tissue; tumor growth; emerging role; size; insulin resistance; nanoparticle tracking analysis; myocardial infarction; circulating microparticles; cardiovascular disease; differentiation; pathogenesis; intercellular communication; in vivo; messenger RNAs; flow cytometry; mediated transfer; stromal cells; nanoparticles; T cells; transferrin receptor; tumor derived exosome; endothelial cells; drug delivery; membrane vesicles; delivery; dendritic cells; proteomic analysis; gene expression; inflammation; microparticles; cell derived exosome; in vitro; stem cells; mesenchymal stem cells; extracellular vesicles
#2 exosome	aptasensor; amplification; heterogeneity; KRAS; exosomal miRNA; chip; women; cell-free DNA; biopsy; tumor cells; mortality; target; nucleic acids; precision medicine; clinical significance; recurrence; DNA methylation; cell lung cancer system; chemotherapy; early diagnosis; mutations; bladder cancer; cancer diagnosis; marker; potential biomarker; cell free DNA; separation; free DNA; classification; management; prognosis; circulating tumor DNA; quantification; peripheral blood; circulating exosome; diagnostic biomarkers; gene; ovarian cancer; risk; survival; blood; pancreatic cancer; messenger RNA; DNA; lung cancer; circulating tumor cells; prostate cancer; breast cancer; liquid biopsy
#3 extracellular vesicles	progress; glioblastoma; diabetic nephropathy; head; discovery; platform; proteomics; genes; reveals; fibrosis; injury; miRNA; extracellular vesicles (EVs); receptor; exosome isolation; biology; communication; mass spectrometry; miRNAs; release; therapy; markers; mechanisms; mechanism; vesicles; activation; disease; secretion; microRNA; RNA; extracellular vesicle; circulating microRNAs; proteins; protein; serum; biomarker; plasma; biogenesis; diagnosis; identification; microRNAs; cancer; microvesicles; cells; biomarkers; expression; exosome
#4 Alzheimer’s disease	cognitive impairment; neuronal exosome; Tau; children; infection; dementia; blood brain barrier; multiple sclerosis; binding; dysfunction; amyloid beta; central nervous system; model; cell; small extracellular vesicles; alpha synuclein; association; Parkinson’s disease; brain; oxidative stress; cerebrospinal fluid; Alzheimer’s disease
#5 plasma diagnostics-interferometry	deposition; density; spectroscopy and imaging; plasma diagnostics-interferometry; temperature; plasma diagnostics; diagnostics

Cluster	Author	Journal	DOI	Most influential paper	Citation
#1	Valadi H	Nature Cell Biology	10.1038/ncb1596	Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells	2620
	Raposo G	Curr Opin Biotech	10.1083/jcb.201211138.	Extracellular vesicles: exosomes, microvesicles, and friends	1840
	Skog J	Nat Cell Biol	10.1038/ncb1800	Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers	1459
#2	Théry C	J Extracell Vesicles	10.1080/20013078.2018.1535750	Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines	2380
	Kalluri R	Science	10.1126/science. aau6977.	The biology, function, and biomedical applications of exosomes	1788
	Van Niel G	Nat Rev Mol Cell Bio	10.1038/nrm.2017.125	Shedding light on the cell biology of extracellular vesicles	1492
#3	Melo S A	Nature	10.1038/nature14581	Glypican-1 identifies cancer exosomes and detects early pancreatic cancer	1176
	Hoshino A	Nature	10.1038/nature15756	Tumour exosome integrins determine organotropic metastasis	1115