DNA methylation detection technology and plasma-based methylation biomarkers in screening of gastrointestinal carcinoma

Epigenomics ◽  
2021 ◽  
Author(s):  
Mengjiao Cao ◽  
Chuanfeng Zhang ◽  
Linfu Zhou
Keyword(s):  
Dna Methylation ◽  
Early Cancer ◽  
High Sensitivity ◽  
Global Burden ◽  
Clinical Tool ◽  
Early Screening ◽  
Gastrointestinal Carcinoma ◽  
Detection Technology ◽  
Potential Biomarker ◽  
Detection Technologies

DNA methylation is of paramount importance for the evolution of human cancers. Its high sensitivity and specificity make it a potential biomarker for early cancer screening in the context of an increasing global burden of gastrointestinal (GI) carcinoma. More DNA methylation biomarkers are emerging with the development of liquid biopsy and sensitive DNA methylation detection technology. This review provides an overview of DNA methylation, focusing on the presentation and comparison of 5-methylcytosine detection technologies, and introduces the promising plasma-based cell-free DNA (cfDNA) methylation biomarkers published in recent years for early screening of GI carcinoma. Finally, we summarize and discuss the future of plasma cfDNA methylation markers detection as a clinical tool for early screening of GI carcinoma.

scholarly journals Genome-wide analysis of DNA methylation identifies two CpG sites for the early screening of colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 37-52 ◽  
Author(s):  
Xiaokang Wang ◽  
Danwen Wang ◽  
Haoran Zhang ◽  
Maohui Feng ◽  
Xiongzhi Wu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
High Sensitivity ◽  
High Specificity ◽  
Diagnostic Model ◽  
Early Screening ◽  
Global Methylation ◽  
Crc Screening ◽  
Genome Wide ◽  
Bowel Diseases

Aim: To identify a panel of DNA methylation markers for the early diagnosis of colorectal cancer (CRC). Materials & methods: Using public omics data and our pyrosequencing data, we developed and validated a global methylation model and a CpG-methylation-based model for CRC screening. Results: Both of the models yielded high sensitivity and specificity for distinguishing CRC and its precursors (colorectal adenoma and colorectal laterally spreading tumor) from normal controls in eight independent datasets and our newly collected samples. More importantly, the two-CpG-based model showed high specificity in excluding inflammatory bowel diseases and other 13 cancer types. Conclusion: A diagnostic model based on two CpGs (cg09239744 and cg12587766) may be a powerful tool for CRC screening.

High Sensitivity C-Reactive Protein as a Potential Biomarker of Neuroinflammation in Major Psychiatric Disorders

2018 ◽  
Vol 14 (2) ◽  
pp. 105-128
Author(s):  
Giordano Padovan ◽  
Rosa Preteroti ◽  
Beatrice Bortolato ◽  
Maria Magdalini Papaioannou ◽  
Giada Piva ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
High Sensitivity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Potential Biomarker

scholarly journals BIOM-62 SENSITIVE DETECTION AND DISCRIMINATION OF INTRACRANIAL TUMORS BY BLOOD

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Farshad Nassiri ◽  
Ankur Chakravarthy ◽  
Shengrui Feng ◽  
Roxana Shen ◽  
Romina Nejad ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Tumors ◽  
Model Performance ◽  
High Sensitivity ◽  
Circulating Tumor Dna ◽  
Low Grade ◽  
Learning Approaches ◽  
Intracranial Tumors ◽  
Cell Of Origin ◽  
Tumor Dna

Abstract BACKGROUND The diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Non-invasive diagnostic approaches, particularly for patients with brain tumours, provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. We reasoned that DNA methylation profiles of circulating tumor DNA in blood can be used as a clinically useful biomarker for patients with brain tumors, given the specificity of DNA methylation profiles for cell-of-origin. METHODS We generated methylation profiles on the plasma of 608 patients with cancer (219 intracranial, 388 extracranial) and 60 healthy controls using a cell-free methylated DNA immunoprecipitation combined with deep sequencing (cfMeDIP-seq) approach. Using machine-learning approaches we generated and evaluated models to distinguish brain tumors from extracranial cancers that may metastasize to the brain, as well as additional models to discriminate common brain tumors included in the differential diagnosis of solitary extra-axial and intra-axial tumors. RESULTS We observed high sensitivity and discriminative capacity for our models to distinguish gliomas from other cancerous and healthy patients (AUC=0.99, 95%CI 0.96–1), with similar performance in IDH mutant and wildtype gliomas as well as in lower- and high-grade gliomas. Excluding non-malignant contributors to plasma methylation did not change model performance (AUC=0.982, 95%CI 0.93–1). Models generated to discriminate intracranial tumors from each other also demonstrated high accuracy for common extra-axial tumors (AUCmeningioma=0.89, 95%CI 0.80–0.97; AUChemangiopericytoma=0.95, 95%CI 0.73–1) as well as intra-axial tumors ranging from low-grade indolent glial-neuronal tumors (AUC 0.93, 95%CI 0.80 – 1) to diffuse intra-axial gliomas with distinct molecular composition (AUCIDH-mutant glioma = 0.82, 95%CI 0.66 -0.98; AUCIDH-wildtype-glioma = 0.71, 95%CI 0.53 – 0.9). Plasma cfMeDIP-seq signals originated from corresponding tumor tissue DNA methylation signals (r=0.37, p< 2.2e-16). CONCLUSIONS These results demonstrate the potential for cfMeDIP-seq profiles to not only detect circulating tumor DNA, but to accurately discriminate common intracranial tumors that share cell-of-origin lineages.

scholarly journals Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Nam-Yun Cho ◽  
Ji-Won Park ◽  
Xianyu Wen ◽  
Yun-Joo Shin ◽  
Jun-Kyu Kang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Sensitivity And Specificity ◽  
Stage Iv ◽  
High Sensitivity ◽  
Liquid Biopsies ◽  
Blood Leukocytes ◽  
Marker Panel ◽  
A Genome ◽  
Methylight Assay

Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC.

scholarly journals Nanopore Technology for the Application of Protein Detection

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1942
Author(s):  
Xiaoqing Zeng ◽  
Yang Xiang ◽  
Qianshan Liu ◽  
Liang Wang ◽  
Qianyun Ma ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Detection ◽  
High Sensitivity ◽  
Single Molecule Detection ◽  
Sequence Detection ◽  
Fast Detection ◽  
Material Basis ◽  
Sensing Technology ◽  
Detection Technology ◽  
Structure Recognition

Protein is an important component of all the cells and tissues of the human body and is the material basis of life. Its content, sequence, and spatial structure have a great impact on proteomics and human biology. It can reflect the important information of normal or pathophysiological processes and promote the development of new diagnoses and treatment methods. However, the current techniques of proteomics for protein analysis are limited by chemical modifications, large sample sizes, or cumbersome operations. Solving this problem requires overcoming huge challenges. Nanopore single molecule detection technology overcomes this shortcoming. As a new sensing technology, it has the advantages of no labeling, high sensitivity, fast detection speed, real-time monitoring, and simple operation. It is widely used in gene sequencing, detection of peptides and proteins, markers and microorganisms, and other biomolecules and metal ions. Therefore, based on the advantages of novel nanopore single-molecule detection technology, its application to protein sequence detection and structure recognition has also been proposed and developed. In this paper, the application of nanopore single-molecule detection technology in protein detection in recent years is reviewed, and its development prospect is investigated.

scholarly journals Mid-infrared photoacoustic gas monitoring driven by a gas-filled hollow-core fiber laser

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yazhou Wang ◽  
Yuyang Feng ◽  
Abubakar I. Adamu ◽  
Manoj K. Dasa ◽  
J. E. Antonio-Lopez ◽  
...  
Keyword(s):  
Fiber Laser ◽  
Signal To Noise Ratio ◽  
High Sensitivity ◽  
Laser Source ◽  
High Signal ◽  
Mid Infrared ◽  
Raman Fiber Laser ◽  
Custom Made ◽  
Core Fiber ◽  
Detection Technologies

AbstractDevelopment of novel mid-infrared (MIR) lasers could ultimately boost emerging detection technologies towards innovative spectroscopic and imaging solutions. Photoacoustic (PA) modality has been heralded for years as one of the most powerful detection tools enabling high signal-to-noise ratio analysis. Here, we demonstrate a novel, compact and sensitive MIR-PA system for carbon dioxide (CO2) monitoring at its strongest absorption band by combining a gas-filled fiber laser and PA technology. Specifically, the PA signals were excited by a custom-made hydrogen (H2) based MIR Raman fiber laser source with a pulse energy of ⁓ 18 μJ, quantum efficiency of ⁓ 80% and peak power of ⁓ 3.9 kW. A CO2 detection limit of 605 ppbv was attained from the Allan deviation. This work constitutes an alternative method for advanced high-sensitivity gas detection.

scholarly journals Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Subir Roy Chowdhury ◽  
Cheryl Peltier ◽  
Sen Hou ◽  
Amandeep Singh ◽  
James B. Johnston ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Standard Dose ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Clinical Tool ◽  
Potential Biomarker ◽  
Apoptotic Pathways ◽  
The Impact

Mitochondrial respiration is becoming more commonly used as a preclinical tool and potential biomarker for chronic lymphocytic leukemia (CLL) and activated B-cell receptor (BCR) signaling. However, respiration parameters have not been evaluated with respect to dose of ibrutinib given in clinical practice or the effect of progression on ibrutinib treatment on respiration of CLL cells. We evaluated the impact of low and standard dose ibrutinib on CLL cells from patients treated in vivo on mitochondrial respiration using Oroboros oxygraph. Cytokines CCL3 and CCL4 were evaluated using the Mesoscale. Western blot analysis was used to evaluate the BCR and apoptotic pathways. We observed no difference in the mitochondrial respiration rates or levels of plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4), β-2 microglobulin (β-2 M) and lactate dehydrogenase (LDH) between low and standard doses of ibrutinib. This may confirm why clinical observations of the safety and efficacy of low dose ibrutinib are observed in practice. Of interest, we also observed that the mitochondrial respiration of CLL cells paralleled the increase in β-2 M and LDH at progression. Our study further supports mitochondrial respiration as a biomarker for response and progression on ibrutinib in CLL cells and a valuable pre-clinical tool.

Neutrophil gelatinase-associated lipocalin as a potential biomarker for pulmonary thromboembolism

2019 ◽  
Vol 45 (1) ◽  
pp. 51-56
Author(s):  
Songul Ozyurt ◽  
Mevlut Karatas ◽  
Medeni Arpa ◽  
Bilge Yilmaz Kara ◽  
Hakan Duman ◽  
...  
Keyword(s):  
Predictive Value ◽  
Pulmonary Thromboembolism ◽  
High Sensitivity ◽  
Control Group ◽  
Arterial Blood Gas ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Arterial Blood ◽  
Potential Biomarker ◽  
Healthy Control ◽  
Neutrophil Gelatinase

Abstract Objective Pulmonary thromboembolism (PTE) is a clinical condition that can be lethal unless promptly diagnosed and treated. The objective was to evaluate the significance of serum neutrophil gelatinase-associated lipocalin (NGAL) in the diagnosis of PTE. Materials and methods In this study, 60 patients hospitalized for acute PTE between May 2015 and December 2016 were enrolled. PTE was diagnosed using spiral computed tomography angiography of the thorax. Cardiac enzyme levels, arterial blood gas, and echocardiography measurements were performed. Whole blood samples were drawn to measure serum NGAL before treatment. Results The PTE group comprised 34 women and 26 men, and the healthy control group included 22 women and 18 men. The mean ages of the patient and control groups were 70.3 ± 14.4 years and 69.0 ± 10.2 years, respectively. Serum NGAL was significantly higher in the patients than in the controls (88.6 ± 33.6 vs. 31.7 ± 10.0 ng/mL, p < 0.001, respectively). The optimal NGAL cut-off value was >50 ng/mL, the sensitivity was 100%, specificity was 98.3%, the negative predictive value was 100%, and the positive predictive value was 68%. Conclusion Serum NGAL is a new biomarker with high sensitivity and specificity to detect, diagnose, and exclude PTE.

High serum miR-421 is associated with metabolic dysregulation and inflammation in patients with metabolic syndrome

Epigenomics ◽  
2021 ◽  
Author(s):  
Aécio A Braga ◽  
Raul H Bortolin ◽  
Magda E Graciano-Saldarriaga ◽  
Thiago DC Hirata ◽  
Alvaro Cerda ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
High Sensitivity ◽  
Serum Levels ◽  
High Serum ◽  
Reactive Protein ◽  
Metabolic Dysregulation ◽  
Inflammatory Status ◽  
Potential Biomarker ◽  
Screening Study

Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Patients & methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity C-reactive protein, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.

scholarly journals Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhaoqiang Jiang ◽  
Shibo Ying ◽  
Wei Shen ◽  
Xianglei He ◽  
Junqiang Chen ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Asbestos Exposure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Early Screening ◽  
Receiver Operating Characteristic Curves ◽  
Chinese Populations ◽  
Pleural Plaques ◽  
Potential Biomarker ◽  
Group A

Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.

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