Dataset Information

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

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), cis-regulatory elements, and repetitive elements were developed using the elastic net regularization under a case-control design.

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 IDH1 (encoding isocitrate dehydrogenase) mutation status or other glioma-related pathological features such as TERT, TP53 in the validation set. Furthermore, the 5hmC biomarkers in cfDNA showed the potential as an independent indicator from IDH1 mutation status and worked in synergy with IDH1 mutation to distinguish GBM from WHO II-III gliomas. Exploration of the 5hmC biomarkers for gliomas revealed relevance to glioma biology.

Conclusions

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

SUBMITTER: Cai J

PROVIDER: S-EPMC8209591 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

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

Cai Jiajun J Zeng Chang C Hua Wei W Qi Zengxin Z Song Yanqun Y Lu Xingyu X Li Dongdong D Zhang Zhou Z Cui Xiaolong X Zhang Xin X Yang Zixiao Z Zhang Jinsen J Quan Kai K Zhu Wei W Cai Jiabin J He Chuan C Cheng Shi-Yuan SY Zhang Wei W Mao Ying Y

Neuro-oncology advances 20210101 1

<h4>Background</h4>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).<h4>Methods</h4>We obtained genome-wide 5hmC profiles using the 5hmC-Sea ...[more]

PMID: 34151267

Similar Datasets

Project description:Background: Gastric cancer (GC) remains the third leading cause of cancer death worldwide due to the absence of sensitive and specific biomarkers for its early detection. 5-hydroxymethylcytosine (5hmC)-enriched gene profiles and regions show tissue-specific and tumor specific, and cell-free DNA (cfDNA) 5hmC modification feature sequencing provides a robust tool for gastric cancer detection.Methods: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the 5hmC modification of cfDNA. Significantly differential 5hmC modification genes were identified to construct a gastric cancer diagnostic model. The data set from Gene Expression Omnibus consisted of 61 gastric cancer patients, 90 healthy individuals and 22 benign gastric disease controls was used as an external testing set to test the robustness of the diagnostic model. Results: The vast majority of 5hmC peaks were distributed in the gene body, accounting for more than 90% of the total 5hmC peaks in both the GC and control groups. The diagnostic model was developed based on five different 5hmC modification genes, FBXL7, PDE3A, TPO, SNTG2 and SXBP5. The model could clearly distinguish gastric cancer patients from controls in the training (AUC=0.95, sensitivity=88.6%, specificity=94.3%), validation (AUC=0.87, sensitivity=73.3%, specificity=93.3%) and testing (AUC=0.90, sensitivity=81.9%, specificity=90.2%) sets. The predicted risk scores of the controls were significantly lower than those of GC patients in our own data (P<0.001) or GEO external testing data (P<0.001), but no significant difference was observed between different TNM stage groups (P=0.09 and 0.66). Furthermore, the risk scores of healthy and benign gastric disease controls in the testing set were also not different (P=0.10). Conclusions: The characteristics of 5hmC in cfDNA are specific to GC patients, and the diagnostic model constructed by the 5hmC features of five genes could effectively identify GC patients.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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