Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detectionResearch in context
Su-Fang Qiu,
Qing-Zheng Zhang,
Zi-Yi Wu,
Ming-Zhu Liu,
Qin Ding,
Fu-Ming Sun,
Yin Wang,
Han-Xuan Yang,
Lu Zheng,
Xin Chen,
Lin Wu,
Jian Bai,
Jing-Feng Liu,
Chuan-Ben Chen
Affiliations
Su-Fang Qiu
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
Qing-Zheng Zhang
Berry Oncology Corporation, Beijing, 100102, China
Zi-Yi Wu
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
Ming-Zhu Liu
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
Qin Ding
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
Fu-Ming Sun
Berry Oncology Corporation, Beijing, 100102, China
Yin Wang
Berry Oncology Corporation, Beijing, 100102, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350200, China
Han-Xuan Yang
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
Lu Zheng
Berry Oncology Corporation, Beijing, 100102, China
Xin Chen
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
Lin Wu
Berry Oncology Corporation, Beijing, 100102, China
Jian Bai
Berry Oncology Corporation, Beijing, 100102, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350200, China; Corresponding author. Berry Oncology Corporation, Beijing, 100102, China.
Jing-Feng Liu
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; Corresponding author. Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
Chuan-Ben Chen
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; Corresponding author. Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
Summary: 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.
