Multimodal analysis of cell-free DNA enhances differentiation of early-stage breast cancer from benign lesions and healthy individuals.
| Title: | Multimodal analysis of cell-free DNA enhances differentiation of early-stage breast cancer from benign lesions and healthy individuals. |
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| Authors: | Van TTV; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran TH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen THH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen VTC; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Vo DH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen GTH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen TH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; To KS; Ho Chi Minh City Oncology Hospital, Ho Chi Minh, Vietnam.; Nguyen AL; Ho Chi Minh City Oncology Hospital, Ho Chi Minh, Vietnam.; Tran CHA; Ho Chi Minh City Oncology Hospital, Ho Chi Minh, Vietnam.; Jasmine TX; Medic Medical Center, Ho Chi Minh, Vietnam.; Vo TL; Medic Medical Center, Ho Chi Minh, Vietnam.; Nai THT; Medic Medical Center, Ho Chi Minh, Vietnam.; Tran TT; Medic Medical Center, Ho Chi Minh, Vietnam.; Truong MH; Medic Medical Center, Ho Chi Minh, Vietnam.; Tran NC; Medic Medical Center, Ho Chi Minh, Vietnam.; Le TL; Thai Nguyen National General Hospital, Thai Nguyen, Vietnam.; Nguyen THN; Thai Nguyen National General Hospital, Thai Nguyen, Vietnam.; Tu NH; Buon Ma, Thuot Medical University Hospital, Buon Ma Thuot, Vietnam.; Tran TS; Buon Ma, Thuot Medical University Hospital, Buon Ma Thuot, Vietnam.; Le BT; Can Tho Oncology Hospital, Can Tho, Vietnam.; Tang VP; Can Tho Oncology Hospital, Can Tho, Vietnam.; Nguyen PTN; Da Nang Oncology Hospital, Da Nang, Vietnam.; Nguyen KT; Nghe An Oncology Hospital, Nghe An, Vietnam.; Ho VC; Nghe An Oncology Hospital, Nghe An, Vietnam.; Nguyen XV; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Doan NNT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran TT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran TMT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tran VU; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Le MP; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Vu TL; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tieu BL; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen HTP; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen LHD; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Phan NM; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Van Phan T; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Do TTT; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Dao TH; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Tang HS; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen DS; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Giang H; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Phan MD; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Nguyen HN; Medical Genetics Institute, Ho Chi Minh, Vietnam.; Vo DH; Ho Chi Minh City Oncology Hospital, Ho Chi Minh, Vietnam. hieuvobvub@gmail.com.; Tran LS; Medical Genetics Institute, Ho Chi Minh, Vietnam. leson1808@gmail.com. |
| Source: | BMC biology [BMC Biol] 2025 Aug 20; Vol. 23 (1), pp. 259. Date of Electronic Publication: 2025 Aug 20. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 101190720 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7007 (Electronic) Linking ISSN: 17417007 NLM ISO Abbreviation: BMC Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, c2003- |
| MeSH Terms: | Breast Neoplasms*/diagnosis ; Breast Neoplasms*/genetics ; Breast Neoplasms*/pathology ; Breast Neoplasms*/blood ; Cell-Free Nucleic Acids*/genetics; Biomarkers, Tumor/genetics ; Early Detection of Cancer/methods ; Humans ; Female ; Middle Aged ; Adult ; DNA Methylation ; Aged |
| Abstract: | Background: Breast cancer (BC) remains the second leading cause of cancer-related mortality among women worldwide. Liquid biopsy based on circulating tumor DNA (ctDNA) offers a promising noninvasive approach for early detection; however, differentiating malignant tumors from benign abnormalities remains a significant challenge.; Results: Here, we developed a multimodal approach to analyze cfDNA methylation and fragmentomic patterns in 273 BC patients, 108 individuals with benign breast conditions, and 134 healthy controls. Genome-wide analyses revealed distinct cfDNA copy number alterations and cytosine-enriched cleavage sites in BC patients. Targeted sequencing further revealed unique methylation patterns, including hypermethylation in GPR126, KLF3, and TLR10 and hypomethylation in TOP1 and MAFB. Our machine-learning model achieved an AUC of 0.90, with 93.6% specificity and 62.1-66.3% sensitivity for stage I-II cancers. In symptomatic populations, sensitivities were 50.0%, 68.2%, and 64.7% for BI-RADS categories 3, 4, and 5, respectively, with 96.1% specificity.; Conclusions: These findings underscore the potential of cfDNA biomarkers to enhance BC detection and reduce the rate of unnecessary biopsies.; (© 2025. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: The research protocol was approved by the Ethics Committees of all participating institutions, with ethics review number 294/BVUB-HĐĐĐ for the discovery cohort and 460/HĐĐĐ-ĐHYD for the validation cohort. Informed written consent was obtained from each participant in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors, including LST, DSN, HG, MDP, and HNN, hold equity in Gene Solutions. We confirm that this does not impact on our compliance with the journal's policies regarding data and material sharing. |
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| Contributed Indexing: | Keywords: Benign abnormalities; Breast cancer; CfDNA; Methylation and fragmentomic |
| Substance Nomenclature: | 0 (Cell-Free Nucleic Acids); 0 (Biomarkers, Tumor) |
| Entry Date(s): | Date Created: 20250820 Date Completed: 20250820 Latest Revision: 20250822 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12366216 |
| DOI: | 10.1186/s12915-025-02371-z |
| PMID: | 40830871 |
| Database: | MEDLINE |
Journal Article