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DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) is the most common type of epigenetically heterogeneous ovarian cancer. Methylation typing has previously been used in many tumour types but not in HGSOC. Methylation typing in HGSOC may promote the development of personalized care. The present study used DNA...

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Autores principales: Wang, Jieyu, Li, Jun, Chen, Ruifang, Yue, Huiran, Li, Wenzhi, Wu, Beibei, Bai, Yang, Zhu, Guohua, Lu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515755/
https://www.ncbi.nlm.nih.gov/pubmed/34645493
http://dx.doi.org/10.1186/s13148-021-01178-3
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author Wang, Jieyu
Li, Jun
Chen, Ruifang
Yue, Huiran
Li, Wenzhi
Wu, Beibei
Bai, Yang
Zhu, Guohua
Lu, Xin
author_facet Wang, Jieyu
Li, Jun
Chen, Ruifang
Yue, Huiran
Li, Wenzhi
Wu, Beibei
Bai, Yang
Zhu, Guohua
Lu, Xin
author_sort Wang, Jieyu
collection PubMed
description High-grade serous ovarian cancer (HGSOC) is the most common type of epigenetically heterogeneous ovarian cancer. Methylation typing has previously been used in many tumour types but not in HGSOC. Methylation typing in HGSOC may promote the development of personalized care. The present study used DNA methylation data from The Cancer Genome Atlas database and identified four unique methylation subtypes of HGSOC. With the poorest prognosis and high frequency of residual tumours, cluster 4 featured hypermethylation of a panel of genes, which indicates that demethylation agents may be tested in this group and that neoadjuvant chemotherapy may be used to reduce the possibility of residual lesions. Cluster 1 and cluster 2 were significantly associated with metastasis genes and metabolic disorders, respectively. Two feature CpG sites, cg24673765 and cg25574024, were obtained through Cox proportional hazards model analysis of the CpG sites. Based on the methylation level of the two CpG sites, the samples were classified into high- and low-risk groups to identify the prognostic information. Similar results were obtained in the validation set. Taken together, these results explain the epigenetic heterogeneity of HGSOC and provide guidance to clinicians for the prognosis of HGSOC based on DNA methylation sites. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01178-3.
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spelling pubmed-85157552021-10-20 DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer Wang, Jieyu Li, Jun Chen, Ruifang Yue, Huiran Li, Wenzhi Wu, Beibei Bai, Yang Zhu, Guohua Lu, Xin Clin Epigenetics Research High-grade serous ovarian cancer (HGSOC) is the most common type of epigenetically heterogeneous ovarian cancer. Methylation typing has previously been used in many tumour types but not in HGSOC. Methylation typing in HGSOC may promote the development of personalized care. The present study used DNA methylation data from The Cancer Genome Atlas database and identified four unique methylation subtypes of HGSOC. With the poorest prognosis and high frequency of residual tumours, cluster 4 featured hypermethylation of a panel of genes, which indicates that demethylation agents may be tested in this group and that neoadjuvant chemotherapy may be used to reduce the possibility of residual lesions. Cluster 1 and cluster 2 were significantly associated with metastasis genes and metabolic disorders, respectively. Two feature CpG sites, cg24673765 and cg25574024, were obtained through Cox proportional hazards model analysis of the CpG sites. Based on the methylation level of the two CpG sites, the samples were classified into high- and low-risk groups to identify the prognostic information. Similar results were obtained in the validation set. Taken together, these results explain the epigenetic heterogeneity of HGSOC and provide guidance to clinicians for the prognosis of HGSOC based on DNA methylation sites. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01178-3. BioMed Central 2021-10-13 /pmc/articles/PMC8515755/ /pubmed/34645493 http://dx.doi.org/10.1186/s13148-021-01178-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Jieyu
Li, Jun
Chen, Ruifang
Yue, Huiran
Li, Wenzhi
Wu, Beibei
Bai, Yang
Zhu, Guohua
Lu, Xin
DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title_full DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title_fullStr DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title_full_unstemmed DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title_short DNA methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
title_sort dna methylation-based profiling reveals distinct clusters with survival heterogeneity in high-grade serous ovarian cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515755/
https://www.ncbi.nlm.nih.gov/pubmed/34645493
http://dx.doi.org/10.1186/s13148-021-01178-3
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