Diagnostic Role of Cell-free DNA Integrity in Thyroid Cancer Particularly for Bethesda IV Cytology

Higazi, Aliaa M.; Hini, Sahar H. El; El-Sharkawy, Esmat; Gayyed, Mariana Fathy; Aziz, Noha A.; Matta, Ragaa Abdelshaheed

doi:10.1016/j.eprac.2021.02.005

Cited by 7 publications

(10 citation statements)

References 29 publications

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“…The technically similar study by H”gazi’et al [ 44 ] found that concentrations of the qPCR amplicons and the integrity index were higher in thyroid malignancies as compared not only with healthy subjects but also with benign goiter. Of note, in the indeterminate Bethesda IV category, specificity for thyroid cancer diagnosis was 100% for the integrity index and 91% for ALU -244 and -83 circulating amounts, respectively.…”

Section: Diagnosticsmentioning

confidence: 81%

“…The majority of studies analyzing cfDNA in thyroid cancer are still based on qPCR [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. However, in recent years, many papers applied NGS [ 45 , 46 , 47 , 48 ] and the dPCR [ 42 , 46 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Cfdna Analysis In Thyroid Cancersmentioning

confidence: 99%

“…Four studies analyzed cfDNA purely quantitative and qualitative parameters in thyroid cancers [ 34 , 35 , 43 , 44 ]. All of them relied on the qPCR amplification of two-length cfDNA fragments.…”

Section: Cfdna Analysis In Thyroid Cancersmentioning

confidence: 99%

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Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management

Marotta

Cennamo

Civita

et al. 2022

Cancers

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Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence trend during the past forty years and a concomitant rise in cancer-related mortality. The circulating cell-free DNA (cfDNA) analysis is a patient’s friendly and repeatable procedure allowing to obtain surrogate information about the genetics and epigenetics of the tumor. The aim of the present review was to address the suitability of cfDNA testing in different forms of thyroid cancer, and the potential clinical applications, as referred to the clinical weaknesses. Despite being limited by the absence of standardization and by reproducibility and validity issues, cfDNA assessment has great potential for the improvement of thyroid cancer management. cfDNA may support the pre-surgical definition of thyroid nodules by complementing invasive thyroid fine needle aspiration cytology. In addition, it may empower risk stratification and could be used as a biomarker for monitoring the post-surgical disease status, both during active surveillance and in the case of anti-tumor treatment.

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Section: Diagnosticsmentioning

confidence: 81%

Section: Cfdna Analysis In Thyroid Cancersmentioning

confidence: 99%

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Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management

Marotta

Cennamo

Civita

et al. 2022

Cancers

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“…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%

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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“…As the size of plasma DNA can be attributed to the caspase-dependent cleavage, nucleosomal organization and chromatin accessibility [ 5 ], the fragmentation profiles of cfDNA are involved with gene expression and multiple other cellular processes [ 6 ]. Therefore, the DNA integrity of cfDNA (cfDI), which is a measure of the extent of cfDNA fragmentation, has been exploited as a biomarker for diagnosis and prognostication in multiple diseases [ 7 , 8 , 9 ]. This is because the index of cfDNA and cfDI, DNA fragments ALU (ALU 115, short fragment and ALU 247, long fragment), and Line1 ( Line1 OFR2, short fragment and Line1 5′UTR, long fragment) have been explored in most diseases, such as infectious diseases, autoimmune disorders, myocardial infarction, and multiple cancers [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis

Qian

Lou

et al. 2022

Cells

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Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE−/− mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS.

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Diagnostic Role of Cell-free DNA Integrity in Thyroid Cancer Particularly for Bethesda IV Cytology

Cited by 7 publications

References 29 publications

Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management

Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management

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

Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis

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