Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detection.

Autor:	Qiu SF; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, 350014, China., Zhang QZ; Berry Oncology Corporation, Beijing, 100102, China., Wu ZY; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China., Liu MZ; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China., Ding Q; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, 350014, China., Sun FM; Berry Oncology Corporation, Beijing, 100102, China., Wang Y; Berry Oncology Corporation, Beijing, 100102, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350200, China., Yang HX; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, 350014, China., Zheng L; Berry Oncology Corporation, Beijing, 100102, China., Chen X; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China., Wu L; Berry Oncology Corporation, Beijing, 100102, China., Bai J; Berry Oncology Corporation, Beijing, 100102, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350200, China. Electronic address: baijian488@berryoncology.com., Liu JF; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, 350014, China. Electronic address: drjingfeng@fjmu.edu.cn., Chen CB; Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China; Fujian Provincial Key Laboratory of Tumor Biotherapy Fuzhou, 350200, China. Electronic address: ccb@fjmu.edu.cn.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Oct; Vol. 108, pp. 105321. Date of Electronic Publication: 2024 Sep 11.
DOI:	10.1016/j.ebiom.2024.105321
Abstrakt:	Background: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). Methods: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability. Findings: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. Interpretation: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. Funding: A full list of funding bodies that contributed to this study can be found in Funding section. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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