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Neurooncol Adv. 2021 Apr 16;3(1):vdab049. doi: 10.1093/noajnl/vdab049. eCollection 2021.

An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects noninvasive diagnostic markers for gliomas.

Neuro-oncology advances

Jiajun Cai, Chang Zeng, Wei Hua, Zengxin Qi, Yanqun Song, Xingyu Lu, Dongdong Li, Zhou Zhang, Xiaolong Cui, Xin Zhang, Zixiao Yang, Jinsen Zhang, Kai Quan, Wei Zhu, Jiabin Cai, Chuan He, Shi-Yuan Cheng, Wei Zhang, Ying Mao

Affiliations

  1. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
  2. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  3. Shanghai Epican Genetech Co., Ltd., Shanghai, China.
  4. Department of Chemistry, The University of Chicago, Chicago, Illinois, USA.
  5. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
  6. The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  7. State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, and The Collaborative Innovation Centre for Brain Science, Fudan University, Shanghai, China.

PMID: 34151267 PMCID: PMC8209591 DOI: 10.1093/noajnl/vdab049

Abstract

BACKGROUND: Gliomas, especially the high-grade glioblastomas (GBM), are highly aggressive tumors in the central nervous system (CNS) with dismal clinical outcomes. Effective biomarkers, which are not currently available, may improve clinical outcomes through early detection. We sought to develop a noninvasive diagnostic approach for gliomas based on 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA).

METHODS: We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 111 prospectively enrolled patients with gliomas and 111 age-, gender-matched healthy individuals, which were split into a training set and a validation set. Integrated models comprised 5hmC levels summarized for gene bodies, long noncoding RNAs (lncRNAs),

RESULTS: The integrated 5hmC-based models differentiated healthy individuals from gliomas (area under the curve [AUC] = 84%; 95% confidence interval [CI], 74-93%), GBM patients (AUC = 84%; 95% CI, 74-94%), WHO II-III glioma patients (AUC = 86%; 95% CI, 76-96%), regardless of

CONCLUSIONS: The 5hmC-Seal in cfDNA offers the promise as a noninvasive approach for effective detection of gliomas in a screening program.

© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Keywords: 5-hydroxymethylcytosine; biomarker; cell-free DNA; diagnosis; glioma

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