5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer
Abstract
:1. Background
2. Methods
2.1. Patients and Sample Collection
2.2. Study Design
2.3. Treatment Response Assessments
2.4. Sample Processing and 5hmC Sequencing Analysis
2.5. Establishing 5hmC Predictive Signatures
2.6. Power and Statistical Analyses
3. Results
3.1. A 5hmC Predictive Signature Is Associated with PFS in ICI-Treated Patients
3.2. The 5hmC Predictive Signature Is Associated with Objective Response Rate
3.3. The 5hmC Predictive Signature Is Associated with Overall Survival in Patients Receiving ICIs
3.4. The 5hmC Predictive Signature Is Associated with Outcomes in Patients Receiving Single-Agent ICI Treatment
3.5. The 5hmC Predictive Signature Is Superior to Tumor PD-L1 Expression for ICI Response Prediction
3.6. The 5hmC Predictive Signature Is Specific to ICI Treatment Prediction
3.7. Genes and Pathways Associated with ICI Treatment Response
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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Responders (No.) | Non-Responders (No.) | Objective Response Rate (95% CI) | ||
---|---|---|---|---|
Training | Low wp-score | 11 | 0 | 100.0% (71.5–100.0%) |
High wp-score | 2 | 8 | 20.0% (2.5–55.6%) | |
Validation | Low wp-score | 9 | 3 | 75.0% (42.8–94.5%) |
High wp-score | 0 | 4 | 0.0% (0.0–60.2%) | |
Test | Low wp-score | 8 | 2 | 80.0% (44.4–97.5%) |
High wp-score | 0 | 8 | 0.0% (0.0–36.9%) | |
Single agent | Low wp-score | 7 | 1 | 87.5% (47.4–99.7%) |
High wp-score | 0 | 7 | 0.0% (0.0–41.0%) |
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Shao, J.; Xu, Y.; Olsen, R.J.; Kasparian, S.; Sun, K.; Mathur, S.; Zhang, J.; He, C.; Chen, S.-H.; Bernicker, E.H.; et al. 5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer. Cells 2024, 13, 715. https://doi.org/10.3390/cells13080715
Shao J, Xu Y, Olsen RJ, Kasparian S, Sun K, Mathur S, Zhang J, He C, Chen S-H, Bernicker EH, et al. 5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer. Cells. 2024; 13(8):715. https://doi.org/10.3390/cells13080715
Chicago/Turabian StyleShao, Jianming, Yitian Xu, Randall J. Olsen, Saro Kasparian, Kai Sun, Sunil Mathur, Jun Zhang, Chuan He, Shu-Hsia Chen, Eric H. Bernicker, and et al. 2024. "5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer" Cells 13, no. 8: 715. https://doi.org/10.3390/cells13080715