The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma

Aim: We investigated whether a difference exists between <i>TSHR, PTEN</i> and <i>RASSF1A</i> methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC)....

Full description

Bibliographic Details
Main Authors: Raimonda Klimaitė, Mintautė Kazokaitė, Aistė Kondrotienė, Dalia Daukšienė, Rasa Sabaliauskaitė, Kristina Žukauskaitė, Birutė Žilaitienė, Sonata Jarmalaitė, Albertas Daukša
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/16/4917
_version_ 1797409520248422400
author Raimonda Klimaitė
Mintautė Kazokaitė
Aistė Kondrotienė
Dalia Daukšienė
Rasa Sabaliauskaitė
Kristina Žukauskaitė
Birutė Žilaitienė
Sonata Jarmalaitė
Albertas Daukša
author_facet Raimonda Klimaitė
Mintautė Kazokaitė
Aistė Kondrotienė
Dalia Daukšienė
Rasa Sabaliauskaitė
Kristina Žukauskaitė
Birutė Žilaitienė
Sonata Jarmalaitė
Albertas Daukša
author_sort Raimonda Klimaitė
collection DOAJ
description Aim: We investigated whether a difference exists between <i>TSHR, PTEN</i> and <i>RASSF1A</i> methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in <i>TSHR, PTEN</i> and <i>RASSF1A</i> genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of <i>TSHR</i> was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (<i>p</i> = 0.040). <i>TSHR</i> methylation levels in the PTC group plasma samples were significantly higher compared to HC (<i>p</i> = 0.022). After surgery, PTC plasma samples showed lower <i>TSHR</i> and <i>PTEN</i> methylation levels compared to the levels before surgery (<i>p</i> = 0.003, <i>p</i> = 0.031, respectively). The <i>TSHR</i> methylation level was significantly higher in PTC with larger tumor size (>2 cm) (<i>p</i> < 0.001), and lymph node metastases (<i>p</i> = 0.01), lymphovascular invasion (<i>p</i> = 0.02) and multifocality (<i>p</i> = 0.013) 0ROC analysis revealed that the <i>TSHR</i> methylation level provides high accuracy in distinguishing PTC from HC (<i>p</i> = 0.022, AUC of 0.616). Conclusion: <i>TSHR</i> methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.
first_indexed 2024-03-09T04:16:15Z
format Article
id doaj.art-251af1c0a58542ad8286fe28b8cdd884
institution Directory Open Access Journal
issn 2077-0383
language English
last_indexed 2024-03-09T04:16:15Z
publishDate 2022-08-01
publisher MDPI AG
record_format Article
series Journal of Clinical Medicine
spelling doaj.art-251af1c0a58542ad8286fe28b8cdd8842023-12-03T13:53:24ZengMDPI AGJournal of Clinical Medicine2077-03832022-08-011116491710.3390/jcm11164917The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid CarcinomaRaimonda Klimaitė0Mintautė Kazokaitė1Aistė Kondrotienė2Dalia Daukšienė3Rasa Sabaliauskaitė4Kristina Žukauskaitė5Birutė Žilaitienė6Sonata Jarmalaitė7Albertas Daukša8Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, LithuaniaInstitute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, LithuaniaInstitute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, LithuaniaInstitute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, 50009 Vilnius, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, 50009 Vilnius, LithuaniaInstitute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50009 Kaunas, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, 50009 Vilnius, LithuaniaInstitute of Digestive Research, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, LithuaniaAim: We investigated whether a difference exists between <i>TSHR, PTEN</i> and <i>RASSF1A</i> methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in <i>TSHR, PTEN</i> and <i>RASSF1A</i> genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of <i>TSHR</i> was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (<i>p</i> = 0.040). <i>TSHR</i> methylation levels in the PTC group plasma samples were significantly higher compared to HC (<i>p</i> = 0.022). After surgery, PTC plasma samples showed lower <i>TSHR</i> and <i>PTEN</i> methylation levels compared to the levels before surgery (<i>p</i> = 0.003, <i>p</i> = 0.031, respectively). The <i>TSHR</i> methylation level was significantly higher in PTC with larger tumor size (>2 cm) (<i>p</i> < 0.001), and lymph node metastases (<i>p</i> = 0.01), lymphovascular invasion (<i>p</i> = 0.02) and multifocality (<i>p</i> = 0.013) 0ROC analysis revealed that the <i>TSHR</i> methylation level provides high accuracy in distinguishing PTC from HC (<i>p</i> = 0.022, AUC of 0.616). Conclusion: <i>TSHR</i> methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.https://www.mdpi.com/2077-0383/11/16/4917papillary thyroid carcinomaPTCmethylation<i>TSHR</i><i>PTEN</i><i>RASSF1A</i>
spellingShingle Raimonda Klimaitė
Mintautė Kazokaitė
Aistė Kondrotienė
Dalia Daukšienė
Rasa Sabaliauskaitė
Kristina Žukauskaitė
Birutė Žilaitienė
Sonata Jarmalaitė
Albertas Daukša
The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
Journal of Clinical Medicine
papillary thyroid carcinoma
PTC
methylation
<i>TSHR</i>
<i>PTEN</i>
<i>RASSF1A</i>
title The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
title_full The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
title_fullStr The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
title_full_unstemmed The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
title_short The Role of <i>TSHR, PTEN</i> and <i>RASSF1A</i> Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
title_sort role of i tshr pten i and i rassf1a i promoters methylation status for non invasive detection of papillary thyroid carcinoma
topic papillary thyroid carcinoma
PTC
methylation
<i>TSHR</i>
<i>PTEN</i>
<i>RASSF1A</i>
url https://www.mdpi.com/2077-0383/11/16/4917
work_keys_str_mv AT raimondaklimaite theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT mintautekazokaite theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT aistekondrotiene theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT daliadauksiene theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT rasasabaliauskaite theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT kristinazukauskaite theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT birutezilaitiene theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT sonatajarmalaite theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT albertasdauksa theroleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT raimondaklimaite roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT mintautekazokaite roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT aistekondrotiene roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT daliadauksiene roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT rasasabaliauskaite roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT kristinazukauskaite roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT birutezilaitiene roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT sonatajarmalaite roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma
AT albertasdauksa roleofitshrpteniandirassf1aipromotersmethylationstatusfornoninvasivedetectionofpapillarythyroidcarcinoma