Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer
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PROVIDER: PRJNA1031581 | ENA |
REPOSITORIES: ENA
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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.
2024-12-30 | GSE246110 | GEO
Project description: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 non-invasive 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 of 5hmC levels summarized for gene bodies, long non-coding 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 (AUC [area under the curve] = 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 non-invasive approach for effective detection of gliomas in a screening program.
2021-05-30 | GSE132118 | GEO
Project description:BackgroundGliomas, 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).MethodsWe 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.ResultsThe 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.ConclusionsThe 5hmC-Seal in cfDNA offers the promise as a noninvasive approach for effective detection of gliomas in a screening program.
| S-EPMC8209591 | biostudies-literature
Project description:Diabetic retinopathy (DR) is a common microvascular complication that may cause severe visual impairment and blindness in patients with type 2 diabetes mellitus (T2DM). Early detection of DR will provide opportunities for more treatment options and better control of disease progression. Effective biomarkers, which are not currently available, may improve clinical outcomes through precise diagnosis and prognosis. We sought to develop a non-invasive diagnostic approach for diabetic retinopathy among type 2 diabetes mellitus based on 5-hydroxymethylcytosines (5hmC), an emerging epigenetic marker, in circulating cell-free DNA (cfDNA)
2021-11-20 | GSE140842 | GEO
Project description:DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression, and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-specific epigenetic signatures in cfDNA were identified in different cancers. 5hmC-based biomarkers demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to epigenetic biomarkers from tissue biopsies. This new strategy could lead to the development of an effective blood-based, minimally-invasive cancer diagnosis and prognosis approach.
2017-09-05 | GSE89570 | GEO
Project description:An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects non-invasive diagnostic markers for gliomas
| PRJNA545974 | ENA
Project description:Background: The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC. Methods: Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2,554 Chinese subjects: 1,204 HCC patients, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC), and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularization for feature selection. Results: The 5hmC-Seal data from HCC patients showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer (BCLC) staging system from non-HCC (validation set: AUC = 88.4%; 95% CI, 85.8-91.1%), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumors (e.g., ≤ 2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC = 84.6%; 95% CI, 80.6-88.7%), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (e.g., smoking/alcohol intake history). Conclusions: We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
2019-08-07 | GSE112679 | GEO
Project description:Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.
| S-EPMC10706891 | biostudies-literature
Project description:The pathogenesis of celiac disease (CeD) remains incompletely understood. Traditional diagnostic techniques for CeD include serological testing and endoscopic examination; however, they have limitations. Therefore, there is a need to identify novel noninvasive biomarkers for CeD diagnosis. We analyzed duodenal and plasma samples from CeD patients by four-dimensional data-dependent acquisition (4D-DIA) proteomics. Differentially expressed proteins (DEPs) were identified for functional analysis and to propose blood biomarkers associated with CeD diagnosis. In duodenal and plasma samples, respectively, 897 and 140 DEPs were identified. Combining weighted gene co-expression network analysis(WGCNA) with the DEPs, five key proteins were identified across three machine learning methods. FGL2 and TXNDC5 were significantly elevated in the CeD group, while CHGA expression showed an increasing trend, but without statistical significance. The receiver operating characteristic curve results indicated an area under the curve (AUC) of 0.7711 for FGL2 and 0.6978 for TXNDC5, with a combined AUC of 0.8944. Exploratory analysis using Mfuzz and three machine learning methods identified four plasma proteins potentially associated with CeD pathological grading (Marsh classification): FABP, CPOX, BHMT, and PPP2CB. We conclude that FGL2 and TXNDC5 deserve exploration as potential sensitive, noninvasive diagnostic biomarkers for CeD.
2024-11-15 | PXD057692 | Pride
Project description:BACKGROUND: Long-term complications of type 2 diabetes (T2D), such as macrovascular and microvascular events, are the major causes for T2D-related disability and mortality. A clinically convenient, non-invasive approach for monitoring the development of these complications would improve the overall life quality of patients with T2D and help reduce healthcare burden through preventive interventions. METHODS: A selective chemical labeling strategy for 5-hydroxymethylcytosines (5hmC-Seal) was used to profile genome-wide 5hmCs, an emerging class of epigenetic markers implicated in complex diseases including diabetes, in circulating cell-free DNA (cfDNA) from a collection of Chinese patients (n = 62). Differentially modified 5hmC markers between patients with T2D with and without macrovascular/microvascular complications were analyzed under a case-control design. RESULTS: Statistically significant changes in 5hmC markers were associated with T2D-related macrovascular/microvascular complications, involving genes and pathways relevant to vascular biology and diabetes, including insulin resistance and inflammation. A 16-gene 5hmC marker panel accurately distinguished patients with vascular complications from those without (testing set: AUC = 0.85, 95%CI, 0.73-0.96), outperforming conventional clinical variables such as urinary albumin. In addition, a separate 13-gene 5hmC marker panel could distinguish patients with single complications from those with multiple complications (testing set: AUC = 0.84, 95%CI, 0.68-0.99), showing superiority over conventional clinical variables. CONCLUSIONS: The 5hmC markers in cfDNA reflected the epigenetic changes in patients with T2D who developed macrovascular/microvascular complications. The 5hmC-Seal assay has the potential to be a clinically convenient, non-invasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.
2020-01-31 | GSE125929 | GEO