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

被引：2

作者：

Bao, Hua ^{[1
]}

Yang, Shanshan ^{[1
]}

Chen, Xiaoxi ^{[1
]}

Dong, Guangqiang ^{[2
]}

Mao, Yuan ^{[3
]}

Wu, Shuyu ^{[1
]}

Cheng, Xi ^{[1
]}

Wu, Xuxiaochen ^{[1
]}

Tang, Wanxiangfu ^{[1
]}

Wu, Min ^{[1
]}

Tang, Shiting ^{[1
]}

Liang, Wenhua ^{[4
]}

Wang, Zheng ^{[5
]}

Yang, Liu ^{[6
]}

Liu, Jiaqi ^{[7
]}

Wang, Tao ^{[8
]}

Zhang, Bingzhong ^{[9
]}

Jiang, Kuirong ^{[10
]}

Xu, Qin ^{[11
,12
]}

Chen, Jierong ^{[13
]}

Huang, Hairong ^{[14
]}

Peng, Junjie ^{[15
]}

Xia, Xiaomeng ^{[16
]}

Wu, Yumei ^{[17
]}

Xu, Shun ^{[18
]}

Tao, Ji ^{[19
]}

Chong, Li ^{[20
]}

Zhu, Dongqin ^{[1
]}

Yang, Ruowei ^{[1
]}

Chang, Shuang ^{[1
]}

He, Peng ^{[1
]}

Xu, Xiuxiu ^{[1
]}

Zhang, JinPeng ^{[1
]}

Shen, Yi ^{[1
]}

Jiang, Ya ^{[1
]}

Liu, Sisi ^{[1
]}

Zhang, Xian ^{[1
]}

Wu, Xue ^{[1
]}

Wang, Xiaonan ^{[1
]}

Shao, Yang ^{[1
,21
]}

机构：

[1] Nanjing Geneseeq Technol Inc, Geneseeq Res Inst, Nanjing, Peoples R China

[2] Nanjing Jiangbei New Area Ctr Publ Hlth Serv, Nanjing, Peoples R China

[3] Nanjing Med Univ, Affiliated Hosp 4, Nanjing, Peoples R China

[4] Guangzhou Med Univ, Affiliated Hosp 1, Dept Thorac Surg & Oncol, Guangzhou, Peoples R China

[5] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, Shanghai, Peoples R China

[6] Jiangsu Canc Hosp, Colorectal Ctr, Nanjing, Peoples R China

[7] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China

[8] Nanjing Drum Tower Hosp, Dept Thorac Surg, Nanjing, Peoples R China

[9] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gynecol Oncol, Guangzhou, Peoples R China

[10] Nanjing Med Univ, Affiliated Hosp 1, Pancreas Ctr, Nanjing, Peoples R China

[11] Fujian Canc Hosp, Dept Gynecol, Fuzhou, Fujian, Peoples R China

[12] Fujian Med Univ, Canc Hosp, Fuzhou, Fujian, Peoples R China

[13] Guangdong Prov Peoples Hosp, Dept Clin Lab, Guangzhou, Peoples R China

[14] Eastern Theater Command Hosp, Dept Thorac Surg, Nanjing, Peoples R China

[15] Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai, Peoples R China

[16] Cent South Univ, Xiangya Hosp 2, Dept Gynaecol, Changsha, Peoples R China

[17] Beijing Obstet & Gynecol Hosp, Dept Gynecol Oncol, Beijing, Peoples R China

[18] China Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Shenyang, Peoples R China

[19] Harbin Med Univ, Dept Gastrointestinal Med Oncol, Canc Hosp, Harbin, Peoples R China

[20] Soochow Univ, Peoples Hosp Changzhou 1, Affiliated Hosp 3, Dept Resp Med, Changzhou, Peoples R China

[21] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Peoples R China

来源：

NATURE MEDICINE | 2025年

关键词：

METHYLATION; ORIGIN; PLASMA;

D O I：

10.1038/s41591-025-03735-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：22

共 51 条

[11] Genome-wide cell-free DNA fragmentation in patients with cancer [J].

Cristiano, Stephen ;

Leal, Alessandro ;

Phallen, Jillian ;

Fiksel, Jacob ;

Adleff, Vilmos ;

Bruhm, Daniel C. ;

Jensen, Sarah Ostrup ;

Medina, Jamie E. ;

Hruban, Carolyn ;

White, James R. ;

Palsgrove, Doreen N. ;

Niknafs, Noushin ;

Anagnostou, Valsamo ;

Forde, Patrick ;

Naidoo, Jarushka ;

Marrone, Kristen ;

Brahmer, Julie ;

Woodward, Brian D. ;

Husain, Hatim ;

van Rooijen, Karlijn L. ;

Orntoft, Mai-Britt Worm ;

Madsen, Anders Husted ;

van de Velde, Cornelis J. H. ;

Verheij, Marcel ;

Cats, Annemieke ;

Punt, Cornelis J. A. ;

Vink, Geraldine R. ;

van Grieken, Nicole C. T. ;

Koopman, Miriam ;

Fijneman, Remond J. A. ;

Johansen, Julia S. ;

Nielsen, Hans Jorgen ;

Meijer, Gerrit A. ;

Andersen, Claus Lindbjerg ;

Scharpf, Robert B. ;

Velculescu, Victor E. .

NATURE, 2019, 570 (7761) :385-+

[12]

Curry SJ, 2018, JAMA-J AM MED ASSOC, V320, P674, DOI [10.1001/jama.2018.10897, 10.1097/01.ogx.0000549540.69362.81]

[13] Predictors of overall and test-specific colorectal Cancer screening adherence [J].

Daskalakis, Constantine ;

DiCarlo, Melissa ;

Hegarty, Sarah ;

Gudur, Anuragh ;

Vernon, Sally W. ;

Myers, Ronald E. .

PREVENTIVE MEDICINE, 2020, 133

[14] Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement [J].

Davidson, Karina W. ;

Barry, Michael J. ;

Mangione, Carol M. ;

Cabana, Michael ;

Caughey, Aaron B. ;

Davis, Esa M. ;

Donahue, Katrina E. ;

Doubeni, Chyke A. ;

Krist, Alex H. ;

Kubik, Martha ;

Li, Li ;

Ogedegbe, Gbenga ;

Owens, Douglas K. ;

Pbert, Lori ;

Silverstein, Michael ;

Stevermer, James ;

Tseng, Chien-Wen ;

Wong, John B. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2021, 325 (19) :1965-1977

[15] Methylation in cell-free DNA for early cancer detection [J].

de la Cruz, F. Fece ;

Corcoran, R. B. .

ANNALS OF ONCOLOGY, 2018, 29 (06) :1351-1353

[16] A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA [J].

Doebley, Anna-Lisa ;

Ko, Minjeong ;

Liao, Hanna ;

Cruikshank, A. Eden ;

Santos, Katheryn ;

Kikawa, Caroline ;

Hiatt, Joseph B. ;

Patton, Robert D. ;

De Sarkar, Navonil ;

Collier, Katharine A. ;

Hoge, Anna C. H. ;

Chen, Katharine ;

Zimmer, Anat ;

Weber, Zachary T. ;

Adil, Mohamed ;

Reichel, Jonathan B. ;

Polak, Paz ;

Adalsteinsson, Viktor A. ;

Nelson, Peter S. ;

MacPherson, David ;

Parsons, Heather A. ;

Stover, Daniel G. ;

Ha, Gavin .

NATURE COMMUNICATIONS, 2022, 13 (01)

[17]

Fritz A., 2000, International classification of diseases for oncology

[18] Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies [J].

Gao, Q. ;

Lin, Y. P. ;

Li, B. S. ;

Wang, G. Q. ;

Dong, L. Q. ;

Shen, B. Y. ;

Lou, W. H. ;

Wu, W. C. ;

Ge, D. ;

Zhu, Q. L. ;

Xu, Y. ;

Xu, J. M. ;

Chang, W. J. ;

Lan, P. ;

Zhou, P. H. ;

He, M. J. ;

Qiao, G. B. ;

Chuai, S. K. ;

Zang, R. Y. ;

Shi, T. Y. ;

Tan, L. J. ;

Yin, J. ;

Zeng, Q. ;

Su, X. F. ;

Wang, Z. D. ;

Zhao, X. Q. ;

Nian, W. Q. ;

Zhang, S. ;

Zhou, J. ;

Cai, S. L. ;

Zhang, Z. H. ;

Fan, J. .

ANNALS OF ONCOLOGY, 2023, 34 (05) :486-495

[19] New genomic technologies for multi-cancer early detection: Rethinking the scope of cancer screening [J].

Hackshaw, Allan ;

Clarke, Christina A. ;

Hartman, Anne-Renee .

CANCER CELL, 2022, 40 (02) :109-113

[20]

Jahr S, 2001, CANCER RES, V61, P1659

← 1 2 3 4 5 6 →