Cargando…

Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course

Pleomorphic adenomas (PAs) are the most frequently diagnosed benign salivary gland tumors. Although the majority of PAs are characterized by slow growth, some develop very fast and are more prone to recur. The reason for such differences remains unidentified. In this study, we performed global DNA m...

Descripción completa

Detalles Bibliográficos
Autores principales: Kiwerska, Katarzyna, Kowal-Wisniewska, Ewelina, Ustaszewski, Adam, Bartkowiak, Ewelina, Jarmuz-Szymczak, Malgorzata, Wierzbicka, Malgorzata, Giefing, Maciej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180868/
https://www.ncbi.nlm.nih.gov/pubmed/35682648
http://dx.doi.org/10.3390/ijms23115962
_version_ 1784723625868263424
author Kiwerska, Katarzyna
Kowal-Wisniewska, Ewelina
Ustaszewski, Adam
Bartkowiak, Ewelina
Jarmuz-Szymczak, Malgorzata
Wierzbicka, Malgorzata
Giefing, Maciej
author_facet Kiwerska, Katarzyna
Kowal-Wisniewska, Ewelina
Ustaszewski, Adam
Bartkowiak, Ewelina
Jarmuz-Szymczak, Malgorzata
Wierzbicka, Malgorzata
Giefing, Maciej
author_sort Kiwerska, Katarzyna
collection PubMed
description Pleomorphic adenomas (PAs) are the most frequently diagnosed benign salivary gland tumors. Although the majority of PAs are characterized by slow growth, some develop very fast and are more prone to recur. The reason for such differences remains unidentified. In this study, we performed global DNA methylation profiling using the Infinium Human Methylation EPIC 850k BeadChip Array (Illumina) to search for epigenetic biomarkers that could distinguish both groups of tumors. The analysis was performed in four fast-growing tumors (FGTs) and four slow-growing tumors (SGTs). In all, 85 CpG dinucleotides differentiating both groups were identified. Six CpG tags (cg06748470, cg18413218, cg10121788, cg08249296, cg18455472, and cg19930657) were selected for bisulfite pyrosequencing in the extended group of samples. We confirmed differences in DNA methylation between both groups of samples. To evaluate the potential diagnostic accuracy of the selected markers, ROC curves were constructed. We indicated that CpGs included in two assays showed an area under the curve with an acceptable prognostic value (AUC > 0.7). However, logistic regression analysis allowed us to indicate a more optimal model consisting of five CpGs ((1) cg06748470, (2) cg00600454, (3) CpG located in chr14: 77,371,501–77,371,502 (not annotated in GRCh37/hg19), (4) CpG2 located in chr16: 77,469,589–77,469,590 (not annotated GRCh37/hg19), and (5) cg19930657) with AUC > 0.8. This set of epigenetic biomarkers may be considered as differentiating factors between FGT and SGT during salivary gland tumor diagnosis. However, this data should be confirmed in a larger cohort of samples.
format Online
Article
Text
id pubmed-9180868
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91808682022-06-10 Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course Kiwerska, Katarzyna Kowal-Wisniewska, Ewelina Ustaszewski, Adam Bartkowiak, Ewelina Jarmuz-Szymczak, Malgorzata Wierzbicka, Malgorzata Giefing, Maciej Int J Mol Sci Article Pleomorphic adenomas (PAs) are the most frequently diagnosed benign salivary gland tumors. Although the majority of PAs are characterized by slow growth, some develop very fast and are more prone to recur. The reason for such differences remains unidentified. In this study, we performed global DNA methylation profiling using the Infinium Human Methylation EPIC 850k BeadChip Array (Illumina) to search for epigenetic biomarkers that could distinguish both groups of tumors. The analysis was performed in four fast-growing tumors (FGTs) and four slow-growing tumors (SGTs). In all, 85 CpG dinucleotides differentiating both groups were identified. Six CpG tags (cg06748470, cg18413218, cg10121788, cg08249296, cg18455472, and cg19930657) were selected for bisulfite pyrosequencing in the extended group of samples. We confirmed differences in DNA methylation between both groups of samples. To evaluate the potential diagnostic accuracy of the selected markers, ROC curves were constructed. We indicated that CpGs included in two assays showed an area under the curve with an acceptable prognostic value (AUC > 0.7). However, logistic regression analysis allowed us to indicate a more optimal model consisting of five CpGs ((1) cg06748470, (2) cg00600454, (3) CpG located in chr14: 77,371,501–77,371,502 (not annotated in GRCh37/hg19), (4) CpG2 located in chr16: 77,469,589–77,469,590 (not annotated GRCh37/hg19), and (5) cg19930657) with AUC > 0.8. This set of epigenetic biomarkers may be considered as differentiating factors between FGT and SGT during salivary gland tumor diagnosis. However, this data should be confirmed in a larger cohort of samples. MDPI 2022-05-25 /pmc/articles/PMC9180868/ /pubmed/35682648 http://dx.doi.org/10.3390/ijms23115962 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kiwerska, Katarzyna
Kowal-Wisniewska, Ewelina
Ustaszewski, Adam
Bartkowiak, Ewelina
Jarmuz-Szymczak, Malgorzata
Wierzbicka, Malgorzata
Giefing, Maciej
Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title_full Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title_fullStr Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title_full_unstemmed Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title_short Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course
title_sort global dna methylation profiling reveals differentially methylated cpgs between salivary gland pleomorphic adenomas with distinct clinical course
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180868/
https://www.ncbi.nlm.nih.gov/pubmed/35682648
http://dx.doi.org/10.3390/ijms23115962
work_keys_str_mv AT kiwerskakatarzyna globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT kowalwisniewskaewelina globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT ustaszewskiadam globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT bartkowiakewelina globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT jarmuzszymczakmalgorzata globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT wierzbickamalgorzata globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse
AT giefingmaciej globaldnamethylationprofilingrevealsdifferentiallymethylatedcpgsbetweensalivaryglandpleomorphicadenomaswithdistinctclinicalcourse