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Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer

BACKGROUND: This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. METHODS: A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, a...

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Autores principales: Um, Sang-Won, Kim, Hong Kwan, Kim, Yujin, Lee, Bo Bin, Kim, Dongho, Han, Joungho, Kim, Hojoong, Shim, Young Mog, Kim, Duk-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738682/
https://www.ncbi.nlm.nih.gov/pubmed/29270240
http://dx.doi.org/10.1186/s13148-017-0432-5
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author Um, Sang-Won
Kim, Hong Kwan
Kim, Yujin
Lee, Bo Bin
Kim, Dongho
Han, Joungho
Kim, Hojoong
Shim, Young Mog
Kim, Duk-Hwan
author_facet Um, Sang-Won
Kim, Hong Kwan
Kim, Yujin
Lee, Bo Bin
Kim, Dongho
Han, Joungho
Kim, Hojoong
Shim, Young Mog
Kim, Duk-Hwan
author_sort Um, Sang-Won
collection PubMed
description BACKGROUND: This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. METHODS: A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy specimens using the Infinium HumanMethylation450 BeadChip, and models for prediction of lung cancer were evaluated using TCGA lung cancer data. RESULTS: Four thousand seven hundred and twenty-six CpGs (P < 1.0E-07) that were highly methylated in tumor tissues were identified from 42 lung cancer patients. Ten CpGs were selected for prediction of lung cancer. Genes including the 10 CpGs were classified into three categories: (i) transcription (HOXA9, SOX17, ZNF154, HOXD13); (ii) cell signaling (HBP1, SFRP1, VIPR2); and (iii) adhesion (PCDH17, ITGA5, CD34). Three logistic regression models based on the 10 CpGs classified 897 TCGA primary lung tissues with a sensitivity of 95.0~97.8% and a specificity of 97.4~98.7%. However, the classification performance of the models was very poor in bronchial washing samples: the area under the curve (AUC) was equal to 0.72~0.78. The methylation levels of the 10 CpGs in bronchial biopsy were not significantly different from those in surgically resected tumor tissues (P > 0.05, Wilcoxon rank-sum test). However, their methylation levels were significantly different between paired bronchial biopsy and washing (P < 0.05, Wilcoxon signed-rank test). CONCLUSIONS: The present study suggests that bronchial biopsy specimen may be used as a surrogate for DNA methylation analysis in patient with inoperable lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-017-0432-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-57386822017-12-21 Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer Um, Sang-Won Kim, Hong Kwan Kim, Yujin Lee, Bo Bin Kim, Dongho Han, Joungho Kim, Hojoong Shim, Young Mog Kim, Duk-Hwan Clin Epigenetics Research BACKGROUND: This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. METHODS: A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy specimens using the Infinium HumanMethylation450 BeadChip, and models for prediction of lung cancer were evaluated using TCGA lung cancer data. RESULTS: Four thousand seven hundred and twenty-six CpGs (P < 1.0E-07) that were highly methylated in tumor tissues were identified from 42 lung cancer patients. Ten CpGs were selected for prediction of lung cancer. Genes including the 10 CpGs were classified into three categories: (i) transcription (HOXA9, SOX17, ZNF154, HOXD13); (ii) cell signaling (HBP1, SFRP1, VIPR2); and (iii) adhesion (PCDH17, ITGA5, CD34). Three logistic regression models based on the 10 CpGs classified 897 TCGA primary lung tissues with a sensitivity of 95.0~97.8% and a specificity of 97.4~98.7%. However, the classification performance of the models was very poor in bronchial washing samples: the area under the curve (AUC) was equal to 0.72~0.78. The methylation levels of the 10 CpGs in bronchial biopsy were not significantly different from those in surgically resected tumor tissues (P > 0.05, Wilcoxon rank-sum test). However, their methylation levels were significantly different between paired bronchial biopsy and washing (P < 0.05, Wilcoxon signed-rank test). CONCLUSIONS: The present study suggests that bronchial biopsy specimen may be used as a surrogate for DNA methylation analysis in patient with inoperable lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-017-0432-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-20 /pmc/articles/PMC5738682/ /pubmed/29270240 http://dx.doi.org/10.1186/s13148-017-0432-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Um, Sang-Won
Kim, Hong Kwan
Kim, Yujin
Lee, Bo Bin
Kim, Dongho
Han, Joungho
Kim, Hojoong
Shim, Young Mog
Kim, Duk-Hwan
Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title_full Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title_fullStr Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title_full_unstemmed Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title_short Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer
title_sort bronchial biopsy specimen as a surrogate for dna methylation analysis in inoperable lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738682/
https://www.ncbi.nlm.nih.gov/pubmed/29270240
http://dx.doi.org/10.1186/s13148-017-0432-5
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