scholarly journals Identification of DNA methylation markers for early detection of CRC indicates a role for nervous system-related genes in CRC

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Glenn Rademakers ◽  
Maartje Massen ◽  
Alexander Koch ◽  
Muriel X. Draht ◽  
Nikkie Buekers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nervous System ◽  
Gene Ontology ◽  
Early Detection ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Methylation Marker ◽  
Diagnostic Potential ◽  
Gene Ontology Enrichment

Abstract Purpose Colonoscopy and the fecal immunochemical test (FIT) are currently the most widely used screening modalities for colorectal cancer (CRC), however, both with their own limitations. Here we aim to identify and validate stool-based DNA methylation markers for the early detection of CRC and investigate the biological pathways prone to DNA methylation. Methods DNA methylation marker discovery was performed using The Cancer Genome Atlas (TCGA) colon adenocarcinoma data set consisting of normal and primary colon adenocarcinoma tissue. The performance of the five best candidate markers and a previously identified marker, NDRG4, was evaluated on tissues and whole stool samples of healthy subjects and CRC patients using quantitative MSP assays. The results were compared and combined with FIT data. Finally, pathway and gene ontology enrichment analyses were performed using ToppFun, GOrilla and clusterProfiler. Results GDNF, HAND2, SLC35F3, SNAP91 and SORCS1 were ranked as the best performing markers. Gene combinations of all five markers, NDRG4 and FIT were evaluated to establish the biomarker panel with the highest diagnostic potential, resulting in the identification of GDNF/SNAP91/NDRG4/FIT as the best performing marker panel. Pathway and gene ontology enrichment analyses revealed that genes associated with the nervous system were enriched in the set of best performing CRC-specific biomarkers. Conclusion In silico discovery analysis using TCGA-derived data yielded a novel DNA-methylation-based assay for the early detection of CRC, potentially improving current screening modalities. Additionally, nervous system-related pathways were enriched in the identified genes, indicating an epigenetic regulation of neuronal genes in CRC.

scholarly journals Hypermethylated PCDHGB7 as a Biomarker for Early Detection of Endometrial Cancer in Endometrial Brush Samples and Cervical Scrapings

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiangjing Yuan ◽  
Zhanrui Mao ◽  
Qi Lu ◽  
Peng Xu ◽  
Chengyang Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Predictive Value ◽  
Developed Countries ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Data Sets ◽  
Methylation Marker ◽  
Validation Set

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a “Tao brush”) and cervical scrapes (with a “Pap brush”) for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

Cell-free DNA methylation markers for noninvasive early detection of nasopharyngeal carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14537-e14537
Author(s):  
Dhruvajyoti Roy ◽  
David J Taggart ◽  
Lianghong Zheng ◽  
Dan Liu ◽  
Gen Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Early Detection ◽  
Stage Iv ◽  
Stage I ◽  
The Arctic ◽  
Cell Free Dna ◽  
Methylation Marker ◽  
Free Dna

e14537 Background: Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignancies among populations native to Southeast Asia, the Mediterranean Basin and the Arctic. Early diagnosis of NPC is predicted to improve survival. The identification of cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is an established approach for detecting various cancers. In the present study, we evaluated the performance characteristics of a previously identified NPC methylation marker panel for the diagnosis of nasopharyngeal carcinoma. Methods: Retrospective samples were obtained for 168 subjects, including: 59 subjects diagnosed with NPC (Stage I to IV), 14 subjects diagnosed with benign nasopharyngeal disease and 43 healthy subjects. In addition, sample were obtained for 52 subjects diagnosed with breast, colorectal, liver or lung cancer. Samples were provided to the laboratory blinded for DNA methylation analysis by using the IvyGene Platform. Results: A total of 57 of the 59 samples drawn from subjects with NPC were correctly identified for an overall sensitivity of 97%, with little difference between the sensitivity of detecting Stage I to Stage IV nasopharyngeal carcinoma (range 92% to 100%). For subjects diagnosed with other cancers, 85% of colorectal cancer samples, 82% of lung cancer samples, 93% of both breast cancer and liver cancer samples, were correctly identified as negative for NPC, for a total calculated analytical specificity of 86%. Additionally, all 43 samples drawn from healthy donors and 14 samples drawn from subjects diagnosed with benign nasopharyngeal disease were correctly identified as negative for nasopharyngeal carcinoma for a combined specificity of 100%. Conclusions: The NPC methylation panel was demonstrated to be both sensitive and specific for the detection of nasopharyngeal carcinoma. The potential of cfDNA methylation markers for the early detection of nasopharyngeal carcinoma is predicted to improve patient outcomes through earlier detection of the disease.

scholarly journals Deconvolution of DNA methylation signatures identifies common differentially methylated gene regions on 1p36 across breast cancer subtypes

2017 ◽  
Author(s):  
Alexander J. Titus ◽  
Gregory P. Way ◽  
Kevin C. Johnson ◽  
Brock C. Christensen
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Complex Disease ◽  
Molecular Subtype ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Disease Heterogeneity ◽  
Cancer Subtypes ◽  
Differentially Methylated Gene

ABSTRACTBreast cancer is a complex disease and studying DNA methylation (DNAm) in tumors is complicated by disease heterogeneity. We compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution on each model. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized on chromosome 1p36.3. We also validated seventeen DMGRs in an independent data set. Identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also provide evidence on the importance and potential function of 1p36 in cancer.

scholarly journals epiLiver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC)

2021 ◽  
Author(s):  
David Cheishvili ◽  
Chifat Wong ◽  
Mohammad Karim ◽  
Mohammad Kibria ◽  
Nusrat Jahan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
High Throughput ◽  
Cost Effective ◽  
Gene Expression Omnibus ◽  
Morbidity And Mortality ◽  
Data Repository ◽  
Liquid Biopsies ◽  
Data Set ◽  
Normal Tissues

Abstract Robust cost effective and high-throughput tests for early detection of cancer in otherwise healthy people could potentially revolutionize public-health and the heavy personal and public burden of the morbidity and mortality from cancer. Several studies have delineated tumor specific DNA methylation profiles that could serve as biomarkers for early detection of Hepatocellular Carcinoma (HCC) as well as other cancers in liquid biopsies. Several published DNA methylation markers fail to distinguish HCC DNA from DNA from other tissues and other cancers that are potentially present in plasma. We describe a set of DNA methylation signatures in HCC that are “categorically” distinct from normal tissues and blood DNA methylation profiles. We develop a classifier combined of 4 CG sites that is sufficient to detect HCC in TCGA HCC data set at high accuracy. A single CG site at the F12 gene is sufficient to differentiate HCC samples from thousands of other blood samples, normal tissues and 31 tumors in the TCGA and Gene Expression Omnibus (GEO) data repository (n = 11,704). A “next generation sequencing”-targeted-multiplexed high-throughput assay was developed, which was used to examine in a clinical study plasma samples from HCC, chronic hepatitis B (CHB) patients and healthy controls (n = 398). The sensitivity for HCC detection was 84.5% at a specificity of 95% and AUC of 0.94. Applying this assay for routine follow up of people who are at high risk for developing HCC could have a significant impact on reducing the morbidity and mortality from HCC.

scholarly journals epiLiver a novel tumor specific, high throughput and cost-effective blood test for specific detection of liver cancer (HCC)

2021 ◽  
Author(s):  
David Cheishvili ◽  
Chifat Wong ◽  
Mohammad Mahbubul Karim ◽  
Mohammad Golam Kibria ◽  
Nusrat Jahan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
High Throughput ◽  
Cost Effective ◽  
Gene Expression Omnibus ◽  
Morbidity And Mortality ◽  
Data Repository ◽  
Liquid Biopsies ◽  
Data Set ◽  
Normal Tissues

AbstractRobust cost effective and high-throughput tests for early detection of cancer in otherwise healthy people could potentially revolutionize public-health and the heavy personal and public burden of the morbidity and mortality from cancer. Several studies have delineated tumor specific DNA methylation profiles that could serve as biomarkers for early detection of Hepatocellular Carcinoma (HCC) as well as other cancers in liquid biopsies. Several published DNA methylation markers fail to distinguish HCC DNA from DNA from other tissues and other cancers that are potentially present in plasma. We describe a set of DNA methylation signatures in HCC that are “categorically” distinct from normal tissues and blood DNA methylation profiles. We develop a classifier combined of 4 CG sites that is sufficient to detect HCC in TCGA HCC data set at high accuracy. A single CG site at the F12 gene is sufficient to differentiate HCC samples from thousands of other blood samples, normal tissues and 31 tumors in the TCGA and Gene Expression Omnibus (GEO) data repository (n=11,704). A “next generation sequencing”-targeted-multiplexed high-throughput assay was developed, which was used to examine in a clinical study plasma samples from HCC, chronic hepatitis B (CHB) patients and healthy controls (n=398). The sensitivity for HCC detection was 84.5% at a specificity of 95% and AUC of 0.94. Applying this assay for routine follow up of people who are at high risk for developing HCC could have a significant impact on reducing the morbidity and mortality from HCC.

scholarly journals Promoter Hypermethylation of Tumor-Suppressor Genes p16INK4a, RASSF1A, TIMP3, and PCQAP/MED15 in Salivary DNA as a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 148 ◽  
Author(s):  
Chamikara Liyanage ◽  
Asanga Wathupola ◽  
Sanjayan Muraleetharan ◽  
Kanthi Perera ◽  
Chamindie Punyadeera ◽  
...  
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Early Detection ◽  
Tumor Suppressor Genes ◽  
Promoter Hypermethylation ◽  
Healthy Controls ◽  
Suppressor Genes ◽  
Marker Panel ◽  
Methylation Marker

Silencing of tumor-suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis; hence, TSGs may serve as early tumor biomarkers. We determined the promoter methylation levels of p16INK4a, RASSF1A, TIMP3, and PCQAP/MED15 TSGs in salivary DNA from oral cancer (OC) and oropharyngeal cancer (OPC) patients, using methylation-specific PCR coupled with densitometry analysis. We assessed the association between DNA methylation of individual TSGs with OC and OPC risk factors. The performance and the clinical validity of this quadruple-methylation marker panel were evaluated in discriminating OC and OPC patients from healthy controls using the CombiROC web tool. Our study reports that RASSF1A, TIMP3, and PCQAP/MED15 TSGs were significantly hypermethylated in OC and OPC cases compared to healthy controls. DNA methylation levels of TSGs were significantly augmented by smoking, alcohol use, and betel quid chewing, indicating the fact that frequent exposure to risk factors may drive oral and oropharyngeal carcinogenesis through TSG promoter hypermethylation. Also, this quadruple-methylation marker panel of p16INK4a, RASSF1A, TIMP3, and PCQAP/MED15 TSGs demonstrated excellent diagnostic accuracy in the early detection of OC at 91.7% sensitivity and 92.3% specificity and of OPC at 99.8% sensitivity and 92.1% specificity from healthy controls.

scholarly journals Identification of Methylation Biomarkers for Early Detection of Prostate Cancer

2021 ◽  
Author(s):  
Yiyi Pu ◽  
Chao Li ◽  
Haining Yuan ◽  
Xiaoju Wang
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Early Diagnosis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Prostate Tumors ◽  
Normal Tissues ◽  
Cancer Genome Atlas ◽  
Cancer Types

Abstract Background: DNA methylation has been widely used for development of cancer diagnosis biomarker. However, the clinical translational rate is low. Databases, such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), offer great opportunities for DNA methylation biomarker identification. By taking advantage of the public databases, we aimed to identify cancer specific biomarkers based on DNA methylation level for early detection purpose. Results: We performed a pan-cancer methylation analysis using datasets from TCGA and validated the results using GEO datasets. To identify early-diagnosis biomarkers, we focused on the localized tumors, and identified the biomarkers that can effectively distinguish the localized tumors from normal tissues. After comparing biomarkers for all cancer types, we identified a large group of cancer specific biomarkers. Within all 26 prostate cancer specific biomarkers selected, we confirmed three biomarker sets by multiplex analysis. First, 7 biomarkers (cg26140475, cg24891312, cg24522654, cg21359747, cg03254336, cg12697139, cg19034132) could detect localized prostate tumors from normal tissues (AUC > 0.9). Second, 9 biomarkers (cg17220055, cg26140475, cg24891312, cg09853702, cg22400059, cg16736279, cg27639613, cg06011086, cg00664697) could distinguish between low and high Gleason score prostate tumors (AUC = 0.79). Last, a single biomarker (cg26140475) completely separated prostate tumor from other urinary tumors (AUC = 1). Conclusions: Our study identified and validated a panel of methylation-based biomarkers which could be used for prostate cancer early diagnosis.

scholarly journals N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Peiling Zhang ◽  
Guolong Liu ◽  
Lin Lu
Keyword(s):  
Clustering Analysis ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Immune Microenvironment ◽  
Data Set ◽  
Survival Status ◽  
Tumor Immune Microenvironment

BackgroundColon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.Materials and MethodsThe m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.ResultsWe identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.ConclusionIn this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.

A Novel Prediction of Quaternary Structural Type of Proteins with Gene Ontology

2020 ◽  
Vol 27 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Xuan Xiao ◽  
Wei-Jie Chen ◽  
Wang-Ren Qiu
Keyword(s):  
Gene Ontology ◽  
Feature Extraction ◽  
Extraction Method ◽  
Quaternary Structure ◽  
Structural Type ◽  
Sequence Information ◽  
Prediction System ◽  
Data Set ◽  
Feature Extraction Method ◽  
Prediction Rate

Background: The information of quaternary structure attributes of proteins is very important because it is closely related to the biological functions of proteins. With the rapid development of new generation sequencing technology, we are facing a challenge: how to automatically identify the four-level attributes of new polypeptide chains according to their sequence information (i.e., whether they are formed as just as a monomer, or as a hetero-oligomer, or a homo-oligomer). Objective: In this article, our goal is to find a new way to represent protein sequences, thereby improving the prediction rate of protein quaternary structure. Methods: In this article, we developed a prediction system for protein quaternary structural type in which a protein sequence was expressed by combining the Pfam functional-domain and gene ontology. turn protein features into digital sequences, and complete the prediction of quaternary structure through specific machine learning algorithms and verification algorithm. Results: Our data set contains 5495 protein samples. Through the method provided in this paper, we classify proteins into monomer, or as a hetero-oligomer, or a homo-oligomer, and the prediction rate is 74.38%, which is 3.24% higher than that of previous studies. Through this new feature extraction method, we can further classify the four-level structure of proteins, and the results are also correspondingly improved. Conclusion: After the applying the new prediction system, compared with the previous results, we have successfully improved the prediction rate. We have reason to believe that the feature extraction method in this paper has better practicability and can be used as a reference for other protein classification problems.

Early Detection of Central Nervous System Relapse of Pediatric Leukemia with Measurement of Optic Nerve Sheath Diameter on MRI

2019 ◽  
Vol 15 (2) ◽  
pp. 237-241
Author(s):  
Taner Arpaci ◽  
Barbaros S. Karagun
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Early Detection ◽  
Optic Nerve Sheath Diameter ◽  
Central Nervous System Relapse ◽  
Mri Findings ◽  
Pediatric Leukemia ◽  
Optic Nerves ◽  
Cns Relapse

Background: Leukemia is the most common pediatric malignancy. Central Nervous System (CNS) is the most frequently involved extramedullary location at diagnosis and at relapse. </P><P> Objective: To determine if Magnetic Resonance Imaging (MRI) findings of optic nerves should contribute to early detection of CNS relapse in pediatric leukemia. Methods: Twenty patients (10 boys, 10 girls; mean age 8,3 years, range 4-16 years) with proven CNS relapse of leukemia followed up between 2009 and 2017 in our institution were included. Orbital MRI exams performed before and during CNS relapse were reviewed retrospectively. Forty optic nerves with Optic Nerve Sheaths (ONS) and Optic Nerve Heads (ONH) were evaluated on fat-suppressed T2-weighted TSE axial MR images. ONS diameter was measured from the point 10 mm posterior to the globe. ONS distension and ONH configuration were graded as 0, 1 and 2. Results: Before CNS relapse, right mean ONS diameter was 4.52 mm and left was 4.61 mm which were 5.68 mm and 5.66 mm respectively during CNS relapse showing a mean increase of 25% on right and 22% on left. During CNS relapse, ONS showed grade 0 distension in 15%, grade 1 in 60%, grade 2 in 25% and ONH demonstrated grade 0 configuration in 70%, grade 1 in 25% and grade 2 in 5% of the patients. Conclusion: MRI findings of optic nerves may contribute to diagnose CNS relapse by demonstrating elevated intracranial pressure in children with leukemia.

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