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Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis

Author

Listed:
  • Xiao Zhou

    (Tsinghua University)

  • Zhen Cheng

    (Tsinghua University)

  • Mingyu Dong

    (Tsinghua University)

  • Qi Liu

    (Tsinghua University)

  • Weiyang Yang

    (Tsinghua University)

  • Min Liu

    (Tsinghua University
    Guangdong Second Provincial General Hospital)

  • Junzhang Tian

    (Guangdong Second Provincial General Hospital)

  • Weibin Cheng

    (Guangdong Second Provincial General Hospital)

Abstract

Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring.

Suggested Citation

  • Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35320-3
    DOI: 10.1038/s41467-022-35320-3
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