期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 67, 期 8, 页码 723-730出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2013.06.007
关键词
Cell-free-DNA; Thyroid cancers; Methylation; BRAF; Early diagnosis
资金
- AIRC Foundation
- EuroClone S.p.A.
Purpose: In the latest years, high levels of circulating cell-free DNA (cf-DNA) have been found to be associated with cancer diagnosis and progression, and cf-DNA has become a potential candidate as biomarker for tumor detection. cf-DNA has been investigated in plasma or serum of many tumor patients affected by different malignancies, but not yet in thyroid cancer (TC). Furthermore, in TC cells the capability to metabolize iodine is frequently lost. SLC5A8 and SLC26A4 genes are both involved in the iodine metabolism, and SLC5A8 hypermethylation status is associated with the BRAF(V600E) mutation, which is the most frequent genetic event underlying the development of papillary TC. The aim of our study is the development of a new non-invasive tool for the diagnosis and prognosis of TC based on cf-DNA, SLC5A8 and SLC26A4 hypermethylation, and BRAF(V600E) analysis. Methods: cf-DNA was measured by quantitative real-time PCR in nine cases of anaplastic thyroid cancer (ATC), 58 medullary thyroid cancers (MTC), five of synchronous medullary and follicular thyroid cancers (SMFC), 23 follicular adenomas (FA), 86 papillary thyroid cancers (PTC). A control group of 19 healthy subjects was taken. Moreover, in the PTC group we analyze the state of hypermethylation of SLC5A8 and SLC26A4, BRAF(V600E) mutation, and their involvement in the loss of function of the thyroid. Results: cf-DNA showed a high ability to discriminate healthy individuals from cancer patients. cf-DNA(ALU83) and cf-DNA(ALU244) values were significantly correlated with the histological type of TC (P-value < 0.0001). A significant increase in the amount of cf-DNA(ALU83) and cf-DNA(ALU244) when methylation occurs was observed (P-value = 0.02). A correlation between BRAF(V600E) and cf-DNA(ALU244/ALU83) was also found (P-value = 0.02). Conclusions: According to our experimental results, the panel including cf-DNA, SLC5A8 and SLC26A4 hypermethylation, and BRAF(V600E) analysis appears easy, reproducible, and non-invasive for the diagnosis on TC. Its possible implication in clinical setting remains to be elucidated. (C) 2013 Elsevier Masson SAS. All rights reserved.
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