Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA

doi:10.1016/j.trsl.2023.07.005

科研成果详情

题名	Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA
作者	Chen, Lu 1,2; Ma, Rong 1; Luo, Chang 3; Xie, Qin 1; Ning, Xin 1; Sun, Kaidi 1; Meng, Fanling 1; Zhou, Meng2; Sun, Jie2
发表日期	2023-12
发表期刊	Translational research : the journal of laboratory and clinical medicine 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Article
关键词	low-coverage whole-genome sequencing noninvasive diagnosis ovarian cancer plasma cell-free DNA progression monitoring
其他关键词	SEROUS OVARIAN ; SURVIVAL ; TUMORS
摘要	Ovarian cancer (OV) is the most lethal gynecological malignancy and requires improved early detection methods and more effective intervention to achieve a better prognosis. The lack of sensitive and noninvasive biomarkers with clinical utility remains a challenge. Here, we conducted a genome-wide copy number variation (CNV) profiling analysis using low-coverage whole genome sequencing (LC-WGS) of plasma cfDNA in patients with nonmalignant and malignant ovarian tumors and identified 10 malignancy-specific and 12 late-stage-specific CNV markers from plasma cfDNA LC-WGS data. Concordance analysis indicated a significant correlation of identified CNV markers between CNV profiles of plasma cfDNA and tissue DNA (Pearson's r = 0.64, P = 0.006 for the TCGA cohort and r = 0.51, P = 0.04 for the Dariush cohort). By leveraging these specific CNV markers and machine learning algorithms, we developed robust predictive models showing excellent performance in distinguishing between malignant and nonmalignant ovarian tumors with F1-scores of 0.90 and ranging from 0.75 to 0.99, and prediction accuracy of 0.89 and ranging from 0.66 to 0.98, respectively, as well as between early- and late-stage ovarian tumors with F1-scores of 0.84 and ranging from 0.61 to 1.00, and prediction accuracy of 0.82 and ranging from 0.63 to 0.96 in our institute cohort and other external validation cohorts. Furthermore, we also discovered and validated certain CNV features associated with survival outcomes and platinum-based chemotherapy response in multicenter cohorts. In conclusion, our study demonstrated the clinical utility of CNV profiling in plasma cfDNA using LC-WGS as a cost-effective and accessible liquid biopsy for OV.
资助项目	Beijing Medical Award Fund[YXJL-2021-0577-0421];Beijing Science and Technology Innovation Medical Development Fund[KC2021-JF-0055-01];National Natural Science Foundation of China[62272346];Zhejiang Provincial Natural Science Foundation of China[LY22C060001];
出版者	ELSEVIER SCIENCE INC
ISSN	1878-1810
EISSN	1878-1810
卷号	262 页码:12-24
DOI	10.1016/j.trsl.2023.07.005
页数	13
WOS类目	Medical Laboratory Technology ; Medicine, General & Internal ; Medicine, Research & Experimental
WOS研究方向	Medical Laboratory Technology ; General & Internal Medicine ; Research & Experimental Medicine
WOS记录号	WOS:001106007400001
收录类别	PUBMED ; SCOPUS ; SCIE
在线发表日期	2023-10
URL	查看原文
PubMed ID	37499745
SCOPUSEID	2-s2.0-85166932336
通讯作者地址	[Meng, Fanling]Department of Gynecology,Harbin Medical University Cancer Hospital,Harbin,150081,China ; [Zhou, Meng]School of Biomedical Engineering,Eye Hospital,Wenzhou Medical University,Wenzhou,325027,China
Scopus学科分类	Public Health, Environmental and Occupational Health;Physiology (medical);Biochemistry (medical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/181753
专题	仁济学院_眼视光、生物医学工程学部
通讯作者	Meng, Fanling; Zhou, Meng
作者单位	1.Department of Gynecology,Harbin Medical University Cancer Hospital,Harbin,China; 2.School of Biomedical Engineering,Eye Hospital,Wenzhou Medical University,Wenzhou,China; 3.Department of Birth Control,Red Cross Central Hospital of Harbin,Harbin,China
第一作者单位	仁济学院_眼视光、生物医学工程学部
通讯作者单位	仁济学院_眼视光、生物医学工程学部
推荐引用方式 GB/T 7714	Chen, Lu,Ma, Rong,Luo, Chang,et al. Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA[J]. Translational research : the journal of laboratory and clinical medicine,2023,262:12-24.
APA	Chen, Lu., Ma, Rong., Luo, Chang., Xie, Qin., Ning, Xin., ... & Sun, Jie. (2023). Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA. Translational research : the journal of laboratory and clinical medicine, 262, 12-24.
MLA	Chen, Lu,et al."Noninvasive early differential diagnosis and progression monitoring of ovarian cancer using the copy number alterations of plasma cell-free DNA".Translational research : the journal of laboratory and clinical medicine 262(2023):12-24.