5-Hydroxymethylcytosines in circulating cell-free DNA as a diagnostic biomarker for nasopharyngeal carcinoma

• Published in: European journal of cancer (1990) Vol. 210; p. 114294
• Main Authors: Chen, Bijuan, Wang, Di, Xu, Yun, Guo, Qiaojuan, Pan, Jianji, Yu, Sisi, Fang, Yunxiang, Xiao, Shuxiang, Ruan, Yuanyuan, Yang, Shanshan, Lin, Mingan, Hong, Jinsheng, Zhan, Zhouwei, Lin, Shaojun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2024
• Subjects: 5-hydroxymethylcytosine; 5-Methylcytosine - analogs & derivatives; 5-Methylcytosine - blood; Adult; Aged; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cell-Free Nucleic Acids - blood; cfDNA; Diagnosis; Epigenetics; Female; Humans; Male; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - blood; Nasopharyngeal Carcinoma - diagnosis; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Neoplasms - blood; Nasopharyngeal Neoplasms - diagnosis; Nasopharyngeal Neoplasms - genetics; ROC Curve; Nasopharyngeal carcinoma; Epigenetics; Diagnosis; cfDNA; 5-hydroxymethylcytosine
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2024.114294

To evaluate the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for nasopharyngeal carcinoma (NPC) and to develop a diagnostic model. Genome-wide 5hmC profiles in cfDNA from 174 NPC patients and 146 non-cancer individuals were analyzed using the 5hmC-Seal technique. A cfDNA 5hmC-based diagnostic model to identify NPC patients was developed using least absolute shrinkage and selection operator (LASSO) logistic regression, and performance was evaluated with receiver operating characteristic (ROC) curves and confusion matrices. The 5hmC-Seal data from patients with NPC showed a different genome-wide distribution than non-tumor samples. Our initial analysis revealed a 12-gene-based 5hmC marker panel to be an accurate diagnostic model effectively distinguishing between NPC samples and non-cancerous samples (training set: area under curve (AUC)= 0.97 [95 % CI: 0.94–0.99]; and test set: AUC= 0.93 [95 % CI: 0.88–0.98]) superior to EBV DNA testing. The diagnostic score performed well in differentiating the non-cancer subjects from early-stage NPC (training set: AUC=0.99 [95 % CI: 0.98–1]; test set: AUC=0.98 [95 % CI: 0.95–1]), and advanced-stage NPC (training set: AUC=0.96 [95 % CI: 0.93–0.99]; test set: AUC=0.93 [95 % CI: 0.88–0.98]). Notably, in EBV-negative patients, the diagnostic scores showed excellent capacity for distinguishing EBV-negative patients with NPC from non-cancer subjects in both the training set (AUC= 0.94 [95 % CI: 0.88–1]) and test set (AUC=0.91 [95 % CI: 0.81–1]). 5hmC modifications in cfDNA are promising noninvasive biomarkers for NPC, offering high sensitivity and specificity, particularly for early-stage and EBV-negative NPC. •cfDNA 5hmC profiles differ between NPC and non-tumor samples.•12-gene 5hmC biomarker accurately detects NPC from non-tumor individuals.•5hmC biomarker excels in early-stage (Stage I/II) NPC detection.•5hmC biomarker effectively detects NPC across different EBV statuses.