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Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma
Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenoc...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323093/ https://www.ncbi.nlm.nih.gov/pubmed/37082886 http://dx.doi.org/10.1111/cas.15817 |
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author | Ito, Yuki Usui, Genki Seki, Motoaki Fukuyo, Masaki Matsusaka, Keisuke Hoshii, Takayuki Sata, Yuki Morimoto, Junichi Hata, Atsushi Nakajima, Takahiro Rahmutulla, Bahityar Kaiho, Taisuke Inage, Terunaga Tanaka, Kazuhisa Sakairi, Yuichi Suzuki, Hidemi Yoshino, Ichiro Kaneda, Atsushi |
author_facet | Ito, Yuki Usui, Genki Seki, Motoaki Fukuyo, Masaki Matsusaka, Keisuke Hoshii, Takayuki Sata, Yuki Morimoto, Junichi Hata, Atsushi Nakajima, Takahiro Rahmutulla, Bahityar Kaiho, Taisuke Inage, Terunaga Tanaka, Kazuhisa Sakairi, Yuichi Suzuki, Hidemi Yoshino, Ichiro Kaneda, Atsushi |
author_sort | Ito, Yuki |
collection | PubMed |
description | Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenocarcinoma cases annotated with the predominant histological subtypes and three normal lung cases using the Infinium BeadChip. Unsupervised hierarchical clustering analysis revealed three subgroups with different methylation levels: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME). Micropapillary pattern (MPP)‐predominant cases and those with MPP components were significantly enriched in HME (p = 0.02 and p = 0.03, respectively). HME cases showed a significantly poor prognosis for recurrence‐free survival (p < 0.001) and overall survival (p = 0.006). We identified 365 HME marker genes specifically hypermethylated in HME cases with enrichment of “cell morphogenesis” related genes; 305 IME marker genes hypermethylated in HME and IME, but not in LME, with enrichment “embryonic organ morphogenesis”‐related genes; 257 Common marker genes hypermethylated commonly in all cancer cases, with enrichment of “regionalization”‐related genes. We extracted surrogate markers for each epigenotype and designed pyrosequencing primers for five HME markers (TCERG1L, CXCL12, FAM181B, HOXA11, GAD2), three IME markers (TBX18, ZNF154, NWD2) and three Common markers (SCT, GJD2, BARHL2). DNA methylation profiling using Infinium data was validated by pyrosequencing, and HME cases defined by pyrosequencing results also showed the worse recurrence‐free survival. In conclusion, lung adenocarcinomas are stratified into subtypes with distinct DNA methylation levels, and the high‐methylation subtype correlated with MPP‐predominant cases and those with MPP components and showed a poor prognosis. |
format | Online Article Text |
id | pubmed-10323093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103230932023-07-07 Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma Ito, Yuki Usui, Genki Seki, Motoaki Fukuyo, Masaki Matsusaka, Keisuke Hoshii, Takayuki Sata, Yuki Morimoto, Junichi Hata, Atsushi Nakajima, Takahiro Rahmutulla, Bahityar Kaiho, Taisuke Inage, Terunaga Tanaka, Kazuhisa Sakairi, Yuichi Suzuki, Hidemi Yoshino, Ichiro Kaneda, Atsushi Cancer Sci ORIGINAL ARTICLES Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenocarcinoma cases annotated with the predominant histological subtypes and three normal lung cases using the Infinium BeadChip. Unsupervised hierarchical clustering analysis revealed three subgroups with different methylation levels: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME). Micropapillary pattern (MPP)‐predominant cases and those with MPP components were significantly enriched in HME (p = 0.02 and p = 0.03, respectively). HME cases showed a significantly poor prognosis for recurrence‐free survival (p < 0.001) and overall survival (p = 0.006). We identified 365 HME marker genes specifically hypermethylated in HME cases with enrichment of “cell morphogenesis” related genes; 305 IME marker genes hypermethylated in HME and IME, but not in LME, with enrichment “embryonic organ morphogenesis”‐related genes; 257 Common marker genes hypermethylated commonly in all cancer cases, with enrichment of “regionalization”‐related genes. We extracted surrogate markers for each epigenotype and designed pyrosequencing primers for five HME markers (TCERG1L, CXCL12, FAM181B, HOXA11, GAD2), three IME markers (TBX18, ZNF154, NWD2) and three Common markers (SCT, GJD2, BARHL2). DNA methylation profiling using Infinium data was validated by pyrosequencing, and HME cases defined by pyrosequencing results also showed the worse recurrence‐free survival. In conclusion, lung adenocarcinomas are stratified into subtypes with distinct DNA methylation levels, and the high‐methylation subtype correlated with MPP‐predominant cases and those with MPP components and showed a poor prognosis. John Wiley and Sons Inc. 2023-04-21 /pmc/articles/PMC10323093/ /pubmed/37082886 http://dx.doi.org/10.1111/cas.15817 Text en © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Ito, Yuki Usui, Genki Seki, Motoaki Fukuyo, Masaki Matsusaka, Keisuke Hoshii, Takayuki Sata, Yuki Morimoto, Junichi Hata, Atsushi Nakajima, Takahiro Rahmutulla, Bahityar Kaiho, Taisuke Inage, Terunaga Tanaka, Kazuhisa Sakairi, Yuichi Suzuki, Hidemi Yoshino, Ichiro Kaneda, Atsushi Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title | Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title_full | Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title_fullStr | Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title_full_unstemmed | Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title_short | Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
title_sort | association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323093/ https://www.ncbi.nlm.nih.gov/pubmed/37082886 http://dx.doi.org/10.1111/cas.15817 |
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