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Updated: Aug 8, 2025
Detection of Cell-Free DNA in Blood Plasma Samples of Cancer Patients
Published on: September 9, 2020
Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
The THUNDER study demonstrated that multi-cancer detection blood tests (MCDBT-1/2) can accurately detect six common cancers early. These blood tests show promise in reducing late-stage diagnoses and improving survival rates for various cancers.
Area of Science:
- Oncology
- Genomics
- Biotechnology
Background:
- Early cancer detection is crucial for effective curative treatment.
- The THUNDER study (NCT04820868) investigated a cell-free DNA (cfDNA) methylation-based technology for early cancer detection.
- The technology, enhanced linear-splinter amplification sequencing, aimed to detect and localize six specific cancer types.
Purpose of the Study:
- To evaluate the performance of cfDNA methylation-based technology for early cancer detection.
- To assess the accuracy of two multi-cancer detection blood test (MCDBT-1/2) models in identifying six cancer types.
- To simulate the real-world utility of these models in improving cancer diagnosis and patient survival.
Main Methods:
- A panel of 161,984 CpG sites was constructed and validated using methylome data.
- Two MCDBT models were trained and validated on retrospective cfDNA samples from 1693 participants.
- Prospective validation was performed on an independent cohort of 1010 participants, with subsequent simulations for stage shift and survival benefits.
Main Results:
- MCDBT-1 achieved 69.1% sensitivity and 98.9% specificity in an independent validation set, with 83.2% tissue origin accuracy.
- For early-stage cancers (I-III), MCDBT-1 sensitivity was 59.8%.
- Simulations indicated MCDBT-1 could decrease late-stage cancer incidence by up to 46.4% and increase 5-year survival by over 40%. MCDBT-2 showed higher sensitivity (75.1%) with slightly lower specificity (95.1%).
Conclusions:
- The MCDBT-1/2 models demonstrated significant potential for early cancer detection through blood tests.
- These models exhibit high sensitivity, specificity, and accuracy in predicting cancer origin.
- The study highlights the clinical utility of cfDNA methylation-based tests in improving cancer outcomes.
