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Decelerated DNA methylation age predicts poor prognosis of breast cancer

BACKGROUND: DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS: We retrieved information of 1076 breast cancer patients from Genomic D...

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Autores principales: Ren, Jun-Ting, Wang, Mei-Xia, Su, Yi, Tang, Lu-Ying, Ren, Ze-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191915/
https://www.ncbi.nlm.nih.gov/pubmed/30333003
http://dx.doi.org/10.1186/s12885-018-4884-6
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author Ren, Jun-Ting
Wang, Mei-Xia
Su, Yi
Tang, Lu-Ying
Ren, Ze-Fang
author_facet Ren, Jun-Ting
Wang, Mei-Xia
Su, Yi
Tang, Lu-Ying
Ren, Ze-Fang
author_sort Ren, Jun-Ting
collection PubMed
description BACKGROUND: DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS: We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath’s method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters. RESULTS: The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29–0.92), the third (HR: 0.49; 95%CI: 0.27–0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20–0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14–0.74). In the full follow-up dataset, similar results were obtained. CONCLUSIONS: DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.
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spelling pubmed-61919152018-10-23 Decelerated DNA methylation age predicts poor prognosis of breast cancer Ren, Jun-Ting Wang, Mei-Xia Su, Yi Tang, Lu-Ying Ren, Ze-Fang BMC Cancer Research Article BACKGROUND: DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS: We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath’s method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters. RESULTS: The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29–0.92), the third (HR: 0.49; 95%CI: 0.27–0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20–0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14–0.74). In the full follow-up dataset, similar results were obtained. CONCLUSIONS: DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit. BioMed Central 2018-10-17 /pmc/articles/PMC6191915/ /pubmed/30333003 http://dx.doi.org/10.1186/s12885-018-4884-6 Text en © The Author(s). 2018 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 Article
Ren, Jun-Ting
Wang, Mei-Xia
Su, Yi
Tang, Lu-Ying
Ren, Ze-Fang
Decelerated DNA methylation age predicts poor prognosis of breast cancer
title Decelerated DNA methylation age predicts poor prognosis of breast cancer
title_full Decelerated DNA methylation age predicts poor prognosis of breast cancer
title_fullStr Decelerated DNA methylation age predicts poor prognosis of breast cancer
title_full_unstemmed Decelerated DNA methylation age predicts poor prognosis of breast cancer
title_short Decelerated DNA methylation age predicts poor prognosis of breast cancer
title_sort decelerated dna methylation age predicts poor prognosis of breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191915/
https://www.ncbi.nlm.nih.gov/pubmed/30333003
http://dx.doi.org/10.1186/s12885-018-4884-6
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