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Updated: May 23, 2025
Using Nanoplasmon-Enhanced Scattering and Low-Magnification Microscope Imaging to Quantify Tumor-Derived Exosomes
Published on: May 24, 2019
Exosome biomarkers in breast cancer: Systematic review and meta-analysis
Yurou Kang1, Xiaoqing Cao1, Yujing Fan2
1Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Background:
Breast cancer (BC) has become the primary cancer that threatens women's health and life expectancy. Early diagnosis is crucial for effective treatment and favourable prognosis. As a non-invasive and valuable liquid biopsy method, exosomes are promising for the diagnosis and prognosis of BC. The aim of this meta-analysis is to evaluate the diagnostic and prognostic value of exosome biomarkers in BC.
Methods:
A systematic search of relevant English literature was conducted in PubMed, Web of Science, and Cochrane library until August 2024 (diagnosis) and October 2024 (prognosis). QUADAS-2 and QUAPAS were used to assess the quality of the literature. Summary statistics and analyses of relevant effect sizes were conducted using STATA software. Subgroup analysis and sensitivity analysis were performed to identify potential sources of heterogeneity.
Results:
For diagnosis, a total of 31 articles with 3,778 patients and 2,722 controls were included, the pooled sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristic curve (AUC) of overall exosome biomarkers were 0.89 (95 %CI: 0.86-0.91), 0.87 (95 %CI: 0.85-0.90), and 0.94 (95 %CI: 0.92-0.96), respectively, indicating a high diagnostic value of exosomes in BC patients. Subgroup analysis suggested that miRNAs in exosomes exhibited better diagnostic value compared to proteins and non-miRNAs, the SEN, SPE, and AUC were 0.89 (95 %CI: 0.82-0.93), 0.86 (95 %CI: 0.80-0.90), and 0.92 (95 %CI: 0.90-0.94), respectively. Among all miRNAs, the pooled SEN, SPE, and AUC of miR-21 were 0.86 (95 %CI: 0.67-0.95), 0.90 (95 %CI: 0.78-0.96), and 0.95 (95 %CI: 0.92-0.96), respectively. The diagnostic efficiency was improved when biomarkers were combined as a panel (SEN 0.91 versus 0.87, SPE 0.89 versus 0.86, AUC 0.96 versus 0.91). In terms of prognosis, we retrieved 14 articles with 2,781 patients. The pooled HR of overall survival (OS) and progression-free survival (PFS) were 1.41 (95 %CI: 0.92-1.90) and 4.39 (95 %CI: 1.87-6.91), respectively, indicating exosome biomarkers like soluble HLA-G, miR-1246, miR-155, and PSMA were a predictor of poor PFS in BC patients. Subgroup analysis in OS group revealed a significant association between the overexpression of exosome proteins (soluble HLA-G, AnxA2, NGF, CXCL13) and worse OS in BC patients (HR = 2.91, 95 %CI: 1.36-4.47). Similarly, the overexpression of miR-1246 and miR-155 was associated with worse PFS in BC patients (HR = 4.13, 95 %CI: 1.24-7.03). Moreover, when biomarkers were combined as a panel, the prognostic efficiency significantly improved in OS (HR = 4.05, 95 %CI: 2.26-5.84) outcome.
Conclusion:
The meta-analysis revealed that exosome miR-21 might serve as a promising diagnostic biomarker in BC. Dysregulated exosome proteins and miRNAs could predict poor OS and PFS outcomes, respectively.
