Early detection of multiple cancer types using multidimensional cell-free DNA fragmentomics

IF 58.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Medicine Pub Date : 2025-05-27 DOI:10.1038/s41591-025-03735-2

Hua Bao, Shanshan Yang, Xiaoxi Chen, Guangqiang Dong, Yuan Mao, Shuyu Wu, Xi Cheng, Xuxiaochen Wu, Wanxiangfu Tang, Min Wu, Shiting Tang, Wenhua Liang, Zheng Wang, Liu Yang, Jiaqi Liu, Tao Wang, Bingzhong Zhang, Kuirong Jiang, Qin Xu, Jierong Chen, Hairong Huang, Junjie Peng, Xiaomeng Xia, Yumei Wu, Shun Xu, Ji Tao, Li Chong, Dongqin Zhu, Ruowei Yang, Shuang Chang, Peng He, Xiuxiu Xu, JinPeng Zhang, Yi Shen, Ya Jiang, Sisi Liu, Xian Zhang, Xue Wu, Xiaonan Wang, Yang Shao

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Abstract

The multicancer early detection (MCED) test has the potential to enhance current cancer-screening methods. We evaluated a new MCED test that analyzes plasma cell-free DNA using genetic- and fragmentomics-based features from whole-genome sequencing. The present study included an internal validation cohort of 3,021 patients with cancer and 3,370 noncancer controls, and an independent cohort of 677 patients with cancer and 687 noncancer individuals. The results demonstrated an overall sensitivity of 87.4%, specificity of 97.8% and tissue-of-origin prediction accuracy of 82.4% in the independent validation cohort. Preliminary results from a prospective study of 3,724 asymptomatic participants showed a sensitivity of 53.5% (predominantly early stage cancers) and specificity of 98.1%. These findings indicate that the MCED test has strong potential to improve early cancer detection and support clinical decision-making.

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利用多维无细胞DNA片段组学早期检测多种癌症类型

多癌早期检测（MCED）测试有可能增强当前的癌症筛查方法。我们评估了一种新的MCED测试，该测试使用全基因组测序的基于遗传和片段组学的特征来分析无浆细胞DNA。目前的研究包括一个内部验证队列，包括3021名癌症患者和3370名非癌症对照，以及一个独立队列，包括677名癌症患者和687名非癌症个体。结果显示，在独立验证队列中，总体敏感性为87.4%，特异性为97.8%，组织来源预测准确率为82.4%。一项前瞻性研究的初步结果显示，3724名无症状参与者的敏感性为53.5%（主要是早期癌症），特异性为98.1%。这些发现表明MCED检测在提高早期癌症检测和支持临床决策方面具有很强的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Medicine 医学-生化与分子生物学

CiteScore

100.90

自引率

0.70%

发文量

525

审稿时长

1 months

期刊介绍： Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.