Evaluation of a multimodal ctDNA-based assay for detection of aggressive cancers lacking standard screening tests.

Autor:	Thien Nguyen CV; Medical Genetics Institute, Ho Chi Minh, Vietnam., Hanh Nguyen TH; Medical Genetics Institute, Ho Chi Minh, Vietnam., Vo DH; Medical Genetics Institute, Ho Chi Minh, Vietnam., Vi Van TT; Medical Genetics Institute, Ho Chi Minh, Vietnam., Huong Nguyen GT; Medical Genetics Institute, Ho Chi Minh, Vietnam., Tran TH; Medical Genetics Institute, Ho Chi Minh, Vietnam., Nguyen TH; Medical Genetics Institute, Ho Chi Minh, Vietnam., Khoa Huynh LA; Medical Genetics Institute, Ho Chi Minh, Vietnam., Nguyen TD; Medical Genetics Institute, Ho Chi Minh, Vietnam., Tran NH; University Medical Center HCM, Ho Chi Minh, Vietnam., Thi Ha TM; Department of Medical Genetics, University of Medicine & Pharmacy, Hue University, Vietnam., Quynh Le PT; Department of Medical Genetics, University of Medicine & Pharmacy, Hue University, Vietnam., Truong XL; Department of Internal Medicine, University of Medicine & Pharmacy, Hue University, Vietnam., Nguyen HL; Medical Genetics Institute, Ho Chi Minh, Vietnam., Tran UV; Medical Genetics Institute, Ho Chi Minh, Vietnam., Hoang TQ; Thai Nguyen Central Hospital, Vietnam., Nguyen VB; Nghe An Oncology Hospital, Vietnam., Le VC; Ha Tinh General Hospital, Vietnam., Nguyen XC; Nghe An Maternity-Pediatric Hospital, Vietnam., Phuong Nguyen TM; 108 Military Central Hospital, Vietnam., Nguyen VH; Hanoi Medical University Hospital, Vietnam., Nhat Tran NT; Thu Duc City Hospital, Vietnam., Quynh Dang TN; Military Hospital 175, Vietnam., Tran MH; Thong Nhat Hospital, Vietnam., Nguyen PN; Binh Dan Hospital, Vietnam., Dao TH; Medical Genetics Institute, Ho Chi Minh, Vietnam., Phuc Nguyen HT; Medical Genetics Institute, Ho Chi Minh, Vietnam., Tran NT; University Medical Center HCM, Ho Chi Minh, Vietnam., Phan TV; Medical Genetics Institute, Ho Chi Minh, Vietnam., Nguyen DS; Medical Genetics Institute, Ho Chi Minh, Vietnam., Tang HS; 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., Tran LS; Medical Genetics Institute, Ho Chi Minh, Vietnam.
Jazyk:	angličtina
Zdroj:	Future oncology (London, England) [Future Oncol] 2024 Oct 21, pp. 1-11. Date of Electronic Publication: 2024 Oct 21.
DOI:	10.1080/14796694.2024.2413266
Abstrakt:	Aim: Cancers lacking standard screening (LSS) options account for approximately 70% of cancer-related deaths due to late-stage diagnosis. Circulating tumor DNA (ctDNA) is a promising biomarker for multi-cancer early detection. We previously developed SPOT-MAS, a multimodal ctDNA-based assay analyzing methylation and fragmentomic profiles, effective in detecting common cancers (breast, colorectal, liver, lung and gastric). This study extends the analysis to five LSS cancers: endometrial, esophageal, head and neck, ovarian and pancreatic. Methods: SPOT-MAS was applied to profile cfDNA methylation and fragmentomic patterns in 739 healthy individuals and 135 LSS cancer patients. Results: We identified 347 differentially methylated regions and observed genome-wide hypomethylation across all five LSS cancers. Esophageal and head and neck cancers showed an enrichment of short cfDNA fragments (<150 bp). Eleven 4-mer end motifs were consistently altered in cfDNA fragments across all LSS cancers. Many significant signatures were consistent with previous observations in common cancers. Notably, SPOT-MAS achieved 96.2% specificity and 74.8% overall sensitivity, with a lower sensitivity of 60.7% in early-stage cancers. Conclusion: This proof-of-concept study demonstrates that SPOT-MAS a non-invasive test trained on five common cancer types, could detect a number of LSS cancer cases, potentially complementing existing screening programs.
Databáze:	MEDLINE
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