Dataset Information

Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value.

ABSTRACT: Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients.

SUBMITTER: Citarella A

PROVIDER: S-EPMC10510276 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value.

Citarella Anna A Besharat Zein Mersini ZM Trocchianesi Sofia S Autilio Tanja Milena TM Verrienti Antonella A Catanzaro Giuseppina G Splendiani Elena E Spinello Zaira Z Cantara Silvia S Zavattari Patrizia P Loi Eleonora E Romei Cristina C Ciampi Raffaele R Pezzullo Luciano L Castagna Maria Grazia MG Angeloni Antonio A Elisei Rosella R Durante Cosimo C Po Agnese A Ferretti Elisabetta E

Biomarker research 20230919 1

Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). M ...[more]

PMID: 37726827

Similar Datasets

Project description:BackgroundBreast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear.MethodsImproved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 49 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hypermethylated regions as diagnostic markers for breast cancer was evaluated.ResultsMean size of cfDNA fragments (100-220 bp) mapped to hypomethylated regions decreased more in patients with breast cancer (4.60 bp, 172.33 to 167.73 bp) than in healthy individuals (2.87 bp, 174.54 to 171.67 bp). Furthermore, proportion of short cfDNA fragments (100-150 bp) in hypomethylated regions when compared with it in hypermethylated regions was found to increase more in patients with breast cancer in two independent discovery cohort. The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for breast cancer diagnosis in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity).ConclusionWe identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.

Project description:BackgroundMedullary thyroid carcinoma (MTC) is a rare malignancy originating from aggressive parafollicular C cells that causes 8-13% of thyroid cancer-related deaths despite its low incidence. Calcitonin and carcinoembryonic antigen (CEA) are considered to be important indicators for the diagnosis of MTC, while serum inflammatory markers have been shown to be valuable in the diagnosis and evaluation of a variety of malignant tumors, but the amount of research literature on MTC is still limited. This article aims to assess the value of serum inflammatory markers, CEA and calcitonin in the differential diagnosis of MTC from papillary thyroid carcinoma (PTC), and to explore the risk factors affecting lateral zone lymph node metastasis of MTC and the clinical features that can be predictive of disease-free survival (DFS).MethodsWe retrospectively analyzed 883 patients with PTC and 128 patients with MTC who received care at West China Hospital Sichuan University. The data of clinical characteristics and follow-up results were collected.ResultsIn our cohort, after performing propensity score matching (PSM), there were 117 patients in the MTC group and 436 in the PTC group. Compared with PTC, MTC patients had higher neutrophil-lymphocyte ratio (NLR) (P=0.008), neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) (P=0.03), and CEA values (P<0.001), and no significant differences were found between the remaining baseline characteristics, with CEA having the largest area under the curve (AUC) in the differential diagnosis of PTC and MTC at 0.898 [95% confidence interval (CI): 0.862-0.934, P<0.001]. Univariate and multivariate logistic regression analyses showed that the occurrence of extrathyroidal extension (ETE) [P=0.002, odds ratio (OR): 4.159, 95% CI: 2.734-5.584], calcitonin level >1,000 pg/mL (P=0.002, OR: 4.785, 95% CI: 3.220-6.350) and CEA level (P=0.04, OR: 1.005, 95% CI: 1.000-1.010) were significantly correlated with lateral zone lymph node metastasis in MTC, while platelet-to-lymphocyte ratio (PLR) was a predictor of DFS.ConclusionsPreoperative blood inflammatory indexes, CEA, and calcitonin level may be able to initially identify MTC and PTC. Meanwhile, ETE, CEA, and calcitonin levels are independent risk factors for lymph node metastasis in the lateral zone of the MTC; therefore, surgeons should consider more carefully planning surgery in conjunction with imaging in patients who have these risk factors at the initial visit.

Dataset Information

Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value.

Publications

Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets