Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells
Abstract
:Simple Summary
Abstract
1. Background
2. Methods
2.1. Study Participants and Samples
2.2. Enrichment of Circulating Tumor Cells from Peripheral Blood
2.3. Immunocytochemistry Profiling of CTCs
2.4. Method Development and Optimization
2.5. Analytical Validation
2.6. Case–Control Clinical Study
2.7. Prospective Clinical Study
2.8. Molecular Concordance Study
3. Results
3.1. Method Development and Optimization
3.2. Analytical Validation
3.3. Case–Control Clinical Study
3.4. Prospective Clinical Study
3.5. Molecular Concordance Study
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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EpCAM, PanCK, CD45 | GATA3, PanCK, CD45 | GCDFP15, PanCK, CD45 | Overall | |
---|---|---|---|---|
Analyte stability | 48 h | |||
Recovery 1 | 94.6% | 86.4% | 88.6% | 89.9% |
Limit of detection | 1 cell/mL | |||
Linear range | 1–64 cells/mL | |||
Linearity | R2 ≥ 0.98 | R2 ≥ 0.98 | R2 ≥ 0.98 | R2 ≥ 0.98 |
Sensitivity | 96.0% (86.3%–99.5%) | 98.0% (89.4%–99.9%) | 94.0% (83.5%–98.8%) | 94.0% (83.5%–98.8%) |
Specificity | 100.0% (88.4%–100.0%) | 100.0% (88.4%–100.0%) | 100.0% (88.4%–100.0%) | 100.0% (88.4%–100.0%) |
Accuracy | 97.5% (91.3% to 99.7%) | 98.8% (93.2% to 99.9%) | 96.3% (89.4%–99.2%) | 96.3% (89.4%–99.2%) |
Precision | CV = 4.6% | CV = 3.9% | CV = 3.8% | CV = 4.1% |
Robustness | CV < 5% |
Case–Control Study, Cancer vs. Asymptomatic Specificity: 100.00% (95% CI: 99.87%–100.00%) | Prospective Study, Cancer vs. Benign Specificity: 93.10% (95% CI: 77.23%–99.15%) | |||
---|---|---|---|---|
Sensitivity | Accuracy | Sensitivity | Accuracy | |
Cumulative | 92.07% 95% CI: 91.12%–93.03% | 99.57% 95% CI: 99.34%–99.81% | 94.64% 95% CI: 88.70%–98.01% | 94.33% 95% CI: 89.13%–97.52% |
Stage 0 | 70.00% 95% CI: 34.75%–93.33% | 99.90% 95% CI: 99.70%–99.98% | 87.50% 95% CI: 67.64%–97.34% | 90.57% 95% CI: 79.34%–96.87% |
Stage I | 89.36% 95% CI: 76.90%–96.45% | 99.81% 95% CI: 99.60%–99.94% | 95.83% 95% CI: 78.88%–99.89% | 94.34% 95% CI: 84.34%–98.82% |
Stage II | 95.74% 95% CI: 85.46%–99.48% | 99.91% 95% CI: 99.75%–99.99% | 95.83% 95% CI: 78.88%–99.89% | 94.34% 95% CI: 84.34%–98.82% |
Stage III | 100.0% 95% CI: 88.43%–100.00% | 100.0% 95% CI: 99.87%–100.00% | 95.00% 95% CI: 75.13%–99.87% | 93.88% 95% CI: 83.13%–98.72% |
Stage IV | 100.0% 95% CI: 88.43%–100.00% | 100.0% 95% CI: 99.87%–100.00% | 100.00% 95% CI: 83.16%–100.00% | 95.92% 95% CI: 86.02%–99.50% |
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Crook, T.; Leonard, R.; Mokbel, K.; Thompson, A.; Michell, M.; Page, R.; Vaid, A.; Mehrotra, R.; Ranade, A.; Limaye, S.; et al. Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells. Cancers 2022, 14, 3341. https://doi.org/10.3390/cancers14143341
Crook T, Leonard R, Mokbel K, Thompson A, Michell M, Page R, Vaid A, Mehrotra R, Ranade A, Limaye S, et al. Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells. Cancers. 2022; 14(14):3341. https://doi.org/10.3390/cancers14143341
Chicago/Turabian StyleCrook, Timothy, Robert Leonard, Kefah Mokbel, Alastair Thompson, Michael Michell, Raymond Page, Ashok Vaid, Ravi Mehrotra, Anantbhushan Ranade, Sewanti Limaye, and et al. 2022. "Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells" Cancers 14, no. 14: 3341. https://doi.org/10.3390/cancers14143341
APA StyleCrook, T., Leonard, R., Mokbel, K., Thompson, A., Michell, M., Page, R., Vaid, A., Mehrotra, R., Ranade, A., Limaye, S., Patil, D., Akolkar, D., Datta, V., Fulmali, P., Apurwa, S., Schuster, S., Srinivasan, A., & Datar, R. (2022). Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells. Cancers, 14(14), 3341. https://doi.org/10.3390/cancers14143341