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. 2020 Jan 1;12(524):eaax7533.
doi: 10.1126/scitranslmed.aax7533.

Circulating Tumor DNA Methylation Profiles Enable Early Diagnosis, Prognosis Prediction, and Screening for Colorectal Cancer

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Circulating Tumor DNA Methylation Profiles Enable Early Diagnosis, Prognosis Prediction, and Screening for Colorectal Cancer

Huiyan Luo et al. Sci Transl Med. .

Expression of concern in

  • Editorial expression of concern.
    Smith OM. Smith OM. Sci Transl Med. 2020 Apr 22;12(540):eabb9997. doi: 10.1126/scitranslmed.abb9997. Sci Transl Med. 2020. PMID: 32321869 No abstract available.

Abstract

Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarker in many cancers. Here, we conducted a study to investigate the potential use of ctDNA methylation markers for the diagnosis and prognostication of colorectal cancer (CRC) and used a prospective cohort to validate their effectiveness in screening patients at high risk of CRC. We first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. Then, we applied a machine learning algorithm to develop a predictive diagnostic and a prognostic model using cell-free DNA (cfDNA) samples from a cohort of 801 patients with CRC and 1021 normal controls. The obtained diagnostic prediction model discriminated patients with CRC from normal controls with high accuracy (area under curve = 0.96). The prognostic prediction model also effectively predicted the prognosis and survival of patients with CRC (P < 0.001). In addition, we generated a ctDNA-based molecular classification of CRC using an unsupervised clustering method and obtained two subgroups of patients with CRC with significantly different overall survival (P = 0.011 in validation cohort). Last, we found that a single ctDNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a high-risk population of 1493 participants in a prospective cohort study. Together, our findings showed the value of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of CRC.

Comment in

  • Diagnosis using methylation.
    Sidaway P. Sidaway P. Nat Rev Clin Oncol. 2020 Apr;17(4):196. doi: 10.1038/s41571-020-0334-x. Nat Rev Clin Oncol. 2020. PMID: 31980806 No abstract available.

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