Circulating CtDNA Methylation Quantification of Two DNA Methyl Transferases in Papillary Thyroid Carcinoma

Khatami, Fatemeh; Toolabi, Ladan Teimoori -; Heshmat, Ramin; Shirzad, Nooshin; Saffar, Hiva; Amoli, Mahsa M.; Aghdam, Mohammad Haddadi; Larijani, Bagher; Tavangar, Seyed Mohammad

doi:10.2139/ssrn.3279176

Cited by 2 publications

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“…Fatemeh Khatami [19] M, H. A. [37] 2021 cf-DNAALU83 Mark Lupo [22] 2018 cf-DNA (BRAF, CTNNB1, EGFR, FOXL2, GNAS, KRAS, NRAS, PIK3CA and TP53) More than 5 mutations are considered positive 1 2 12 41 8 Susmita Dutta [14] 2021 Mutation from cf-DNA (BRAF, NRAS, KRAS, HRAS, RET-PTC3, TERT, RET-PTC1, PAX8-PPARɤ) 37 6 0 76 9 Jia Meng [23] 2020 cf-DNAALU115 SiShuang huang [24] 2021 ctDNA 19 11 3 49 11…”

Section: Discussionmentioning

confidence: 99%

“…Of the 20 studies included in this meta-analysis, 4 studies focused on specific mutations in cfDNA, such as circulating BRAF V600E, CTNNB1, EGFR, FOXL2, GNAS, KRAS, NRAS, HRAS, RET-PTC3, TERT, RET-PTC1, PAX8-PPARɤ, PIK3CA, and TP53 mutations [14,17,22,39] ; 4 studies used methylation-sensitive high-resolution melting to identify the methylation status of the promoter regions of genes such as MGMT(C), MGMT(D), SLC5A8(c) and RASSF1(b) [19,21] ; 1 study used methylation-specific PCR to identify the methylation of the TSHR, RARβ2, and RASSF1A genes [25] ; 9 studies used real-time fluorescence qPCR to detect the content of cfDNA, such as the concentrations of cfDNA ALU83 and cfDNA ALU244, in patients with TC [16,18,24,26,27,37] ; and 1 study used qPCR to calculate the numbers of longer and shorter gene fragments in the plasma and then calculate the ratio of the absolute concentrations of longer and shorter fragments, such as qPCR-Alu247 value/qPCR-Alu115 value, to calculate the cfDNA index. [23] Finally, all patients in these 20 studies had cfDNA samples collected prior to surgery.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic value of cell-free DNA in thyroid cancer: A systematic review and meta-analysis

Hou¹,

Sun²,

Deng³

2023

Medicine

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Objective: An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.Methods: A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.Results: A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91. Conclusions:The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.Abbreviations: AUC = area under the curve, BTN = benign thyroid nodule, cfDNA = cell-free DNA, CI = confidence interval, CNKI = China National Knowledge Infrastructure, ctDNA = circulating tumor DNA, DOR = diagnostic odds ratio, HCC = hepatocellular carcinoma, NLR = negative likelihood ratio, PLR = positive likelihood ratio, qPCR = quantitative real-time polymerase chain reaction, SROC = summary receiver operating characteristic, TC = thyroid cancer, Tg = thyroglobulin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Diagnostic value of cell-free DNA in thyroid cancer: A systematic review and meta-analysis

Hou¹,

Sun²,

Deng³

2023

Medicine

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“…In addition, ctDNA methylation is an important epigenetic modification to control tumors, and detection of ctDNA methylation level can effectively determine the degree of malignancy of tumors [46] . The methods for analyzing ctDNA methylation mainly include PCR, sequencing and microarray, etc., but all of these methods require ctDNA pretreatment [47,48] . In contrast, 5-methylcytosinine (5-MC) monoantibodies can be directly immobilized on the electrode by covalently coupling method, which can be used to capture methylated ctDNA without sample pretreatment.…”

Section: Antibody Probe-based Detectionmentioning

confidence: 99%

Electroanalytical Biosensors for Circulating Tumor DNA Detection—A Brief Review

Peng¹,

Lin²,

Nian³

et al. 2021

Preprint

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Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer screening. Consequently, the detection of ctDNA in liquid biopsy gains much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from the industry. However, traditional gene detection technology is difficult to achieve low cost, real-time and portable measurement of ctDNA. Electroanalytical biosensors have many unique advantages such as high sensitivity, high specificity, low cost and good portability. Therefore, this review aims to discuss the latest development of biosensors for minimal-invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, detection strategies and figures of merit. Aiming at the portable, real-time and non-destructive characteristics of biosensors, we analyze their development in the Internet of Things, point-of-care testing, big data and big health.

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Circulating CtDNA Methylation Quantification of Two DNA Methyl Transferases in Papillary Thyroid Carcinoma

Cited by 2 publications

References 0 publications

Diagnostic value of cell-free DNA in thyroid cancer: A systematic review and meta-analysis

Diagnostic value of cell-free DNA in thyroid cancer: A systematic review and meta-analysis

Electroanalytical Biosensors for Circulating Tumor DNA Detection—A Brief Review

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