scholarly journals A novel cell‐free DNA methylation‐based model improves the early detection of colorectal cancer

2021 ◽  
Author(s):  
Xianrui Wu ◽  
Yunfeng Zhang ◽  
Tuo Hu ◽  
Xiaowen He ◽  
Yifeng Zou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Cell Free Dna ◽  
Free Dna

Methylation of FBN1, SPG20, ITF2, RUNX3, SNCA, MLH1, and SEPT9 genes in circulating cell-free DNA as biomarkers of colorectal cancer

2021 ◽  
pp. 1-30
Author(s):  
Maryam Alizadeh-Sedigh ◽  
Mohammad Sadegh Fazeli ◽  
Habibollah Mahmoodzadeh ◽  
Shahin Behrouz Sharif ◽  
Ladan Teimoori-Toolabi
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Diagnostic Performance ◽  
Methylation Status ◽  
Melting Curve ◽  
Melting Curve Analysis ◽  
Promoter Regions ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Tissues

BACKGROUND: Investigating aberrant tumor-specific methylation in plasma cell-free DNA provides a promising and noninvasive biomarker for cancer detection. OBJECTIVE: We aimed to investigate methylation status of some promoter regions in the plasma and tumor tissues to find biomarkers for early detection of colorectal cancer. METHODS: This case-control study on seventy colorectal cancer patients and fifty matched healthy controls used Methylation-Specific High-Resolution Melting Curve analysis to evaluate the methylation of the selected promoter regions in converted genomic tissue DNA and plasma cfDNA. RESULTS: The methylation levels in selected regions of SPG20 (+24375 to +24680, +24209 to +24399, and +23625 to +23883), SNCA (+807 to +1013, +7 to +162, and -180 to +7), FBN1 (+223 to +429, +1 to +245, and -18 to -175), ITF2 (+296 to +436 and -180 to +55), SEPT9 (-914412 to -91590 and -99083 to -92264), and MLH1 (-13 to +22) were significantly higher in tumor tissues compared with normal adjacent tissues. The methylation levels of FBN1, ITF2, SNCA, and SPG20 promoters were significantly higher in the patient’s plasma compared to patient’s normal tissue and plasma of healthy control subjects. FBN1, SPG20, and SEPT9 promoter methylation had a good diagnostic performance for discriminating CRC tissues from normal adjacent tissues (AUC > 0.8). A panel of SPG20, FBN1, and SEPT9 methylation had a higher diagnostic value than that of any single biomarker and other panels in tissue-based assay (AUC > 0.9). The methylation of FBN1(a) and SPG20(a) regions, as the closest region to the first coding sequence (CDS), had a good diagnostic performance in plasma cfDNA (AUC > 0.8) while a panel consisted of FBN1(a) and SPG20(a) regions showed excellent diagnostic performance for CRC detection in plasma cfDNA (AUC > 0.9). CONCLUSION: Methylation of FBN1(a) and SPG20(a) promoter regions in the plasma cfDNA can be an excellent simple, non-invasive blood-based test for early detection of CRC.

EpiPanGI Dx: A cell-free DNA methylation fingerprint for the early detection of gastrointestinal cancers

2021 ◽  
pp. clincanres.1982.2021
Author(s):  
Raju Kandimalla ◽  
Jianfeng Xu ◽  
Alexander Link ◽  
Takatoshi Matsuyama ◽  
Kensuke Yamamura ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
Gastrointestinal Cancers ◽  
Cell Free Dna ◽  
Free Dna ◽  
A Cell

scholarly journals Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women

2018 ◽  
Author(s):  
Carmen Jeronimo ◽  
Sandra Nunes ◽  
Catarina Moreira-Barbosa ◽  
Sofia Salta ◽  
Susana Palma de Sousa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Clinical correlates of circulating cell-free DNA tumor fraction

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256436
Author(s):  
Joerg Bredno ◽  
Jafi Lipson ◽  
Oliver Venn ◽  
Alexander M. Aravanis ◽  
Arash Jamshidi
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Metabolic Activity ◽  
Linear Models ◽  
Circulating Tumor Dna ◽  
Cell Free Dna ◽  
Clinical Correlates ◽  
Cancer Early Detection ◽  
Free Dna ◽  
Tumor Dna

Background Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. Methods and findings Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test. Conclusions Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

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.

Epigenetic biomarkers for noninvasive detection of colorectal cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 45-45
Author(s):  
Dhruvajyoti Roy ◽  
David Taggart ◽  
Lianghong Zheng ◽  
Dan Liu ◽  
Gen Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Stage I ◽  
Cancer Stage ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Epigenetic Biomarkers ◽  
Free Dna ◽  
Diagnostic Potential ◽  
Target Sites

45 Background: Aberrant DNA hypermethylation is known to be a major mechanism for inactivation of cancer-associated genes, including tumor suppressor genes, in colorectal cancer (CRC) and in other human cancers. Cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is a non-invasive method to obtain representative epigenetic information from solid tumors. In the present study, we identified and validated colorectal cancer-specific methylation markers for diagnosis of the disease with high sensitivity and specificity. We also compared the relative amount of DNA methylation at these target sites in relation to colorectal cancer stage. Methods: For marker validation, a total of 154 samples drawn from 68 subjects diagnosed with colorectal cancer (Stage I to IV), 42 healthy donors, 14 subjects with benign colorectal diseases, and 30 subjects diagnosed with other cancer types (breast, liver and lung cancer: 10 cases each) were obtained for a randomized, blinded study. Cell-free DNA was then extracted from the samples, bisulfite converted, and DNA methylation was quantified by using the IvyGene Platform. Results: By quantifying DNA methylation at the target sites, colorectal cancer samples were differentiated from samples drawn from healthy subjects or subjects with benign disease with an overall sensitivity of 93% (95% CI: 86-99) and specificity of 100% (95% CI: 85-100). All stages (I to IV) of colorectal cancer were identified with sensitivities ranging from 67% to 100%. None of the 30 samples drawn from subjects diagnosed with breast, liver or lung cancers were incorrectly identified as a colorectal cancer by the assay, for a calculated analytical specificity of 100%. Conclusions: These results demonstrate the high diagnostic potential of cfDNA methylation markers isolated from blood for the detection of colorectal cancer. Taken together, these findings establish the utility of methylation biomarkers for the detection of colorectal cancers as early as Stage I. In addition, a quantitative analysis of cfDNA provides an opportunity for non-invasive detection and monitoring of disease.

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