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.
Berry Oncology Corporation, Beijing, 100102, China.
EBioMedicine. 2024 Oct;108:105321. doi: 10.1016/j.ebiom.2024.105321. Epub 2024 Sep 11.
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).
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.
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.
We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC.
A full list of funding bodies that contributed to this study can be found in Funding section.
早期发现鼻咽癌（NPC）是一个重大挑战。目前缺乏针对鼻咽癌的高度敏感和特异性诊断生物标志物，这导致了鼻咽癌患者的预后不良。在这里，我们旨在建立一种使用循环无细胞 DNA（cfDNA）检测鼻咽癌的非侵入性方法。
我们研究了外周血细胞的下一代测序（NGS）作为鼻咽癌诊断工具的潜力。我们从 553 名中国受试者中收集了全基因组核小体足迹（NF）、5'端基序、片段模式、CNV 信息和 EBV 含量的数据，其中包括 234 名 NPC 患者和 319 名健康个体。通过病例对照分析，我们为 NPC 开发了一个诊断模型，并验证了其检测能力。
我们的研究结果表明，与健康对照组相比，NPC 患者的 NF、片段和基序频率明显更高。我们基于这些参数开发了一个 NPC 评分，根据美国癌症联合委员会分期系统，该评分能够准确地区分 NPC 与非 NPC 病例（验证集：曲线下面积（AUC）= 99.9%（95%CI：99.8%-100%），特异性：98.15%，敏感性：100%）。该模型在区分 NPC 患者和健康对照组方面的表现优于血浆 EBV DNA。此外，即使在临床治疗后，NPC 评分也能有效区分 NPC 患者和健康对照组。此外，NPC 评分独立于年龄、性别或 TNM 分期等潜在混杂因素。
我们已经开发并验证了一种具有很大临床应用潜力的非侵入性方法来检测 NPC。
该研究的资助机构完整列表可在资助部分找到。
