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A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours
BACKGROUND: Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372264/ https://www.ncbi.nlm.nih.gov/pubmed/28360947 http://dx.doi.org/10.1186/s13148-017-0330-x |
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author | Reddy, Divya Khade, Bharat Pandya, Riddhi Gupta, Sanjay |
author_facet | Reddy, Divya Khade, Bharat Pandya, Riddhi Gupta, Sanjay |
author_sort | Reddy, Divya |
collection | PubMed |
description | BACKGROUND: Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like ‘liquid biopsy’ for analysis of histone modifications and their modifiers if possible will be helpful in the better clinical management of cancer patients. METHODS: Here, we have developed a cost-effective and time-efficient protocol for isolation of circulating histones from serum of solid tumor, HCC, called Dual Acid Extraction (DAE) protocol and have confirmed by mass spectrometry. Also, we measured the activity of HDACs and HATs in serum samples. RESULTS: The serum purified histones were profiled for changes in histone PTMs and have shown a comparable pattern of modifications like acetylation (H4K16Ac), methylation (H4K20Me3, H3K27Me3, H3K9Me3) and phosphorylation (γ-H2AX and H3S10P) to paired cancer tissues. Profiling for the histone PTM changes in various other organs of normal and tumor bearing animal suggests that the changes in the histone PTMs observed in the tumor serum is indeed due to changes in the tumor tissue only. Further, we demonstrate that the observed hypo-acetylation of histone H4 in tissue and serum samples of tumor bearing animals corroborated with the elevated HDAC activity in both samples compared to normal. Interestingly, human normal and tumor serum samples also showed elevated HDAC activity with no significant changes in HAT activity. CONCLUSIONS: Our study provides the first evidence in the context of histone PTMs and modifiers that liquid biopsy is a valuable predictive tool for monitoring disease progression. Importantly, with the advent of drugs that target specific enzymes involved in the epigenetic regulation of gene expression, liquid biopsy-based ‘real time’ monitoring will be useful for subgrouping of the patients for epi-drug treatment, predicting response to therapy, early relapse and prognosis. |
format | Online Article Text |
id | pubmed-5372264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53722642017-03-30 A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours Reddy, Divya Khade, Bharat Pandya, Riddhi Gupta, Sanjay Clin Epigenetics Methodology BACKGROUND: Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like ‘liquid biopsy’ for analysis of histone modifications and their modifiers if possible will be helpful in the better clinical management of cancer patients. METHODS: Here, we have developed a cost-effective and time-efficient protocol for isolation of circulating histones from serum of solid tumor, HCC, called Dual Acid Extraction (DAE) protocol and have confirmed by mass spectrometry. Also, we measured the activity of HDACs and HATs in serum samples. RESULTS: The serum purified histones were profiled for changes in histone PTMs and have shown a comparable pattern of modifications like acetylation (H4K16Ac), methylation (H4K20Me3, H3K27Me3, H3K9Me3) and phosphorylation (γ-H2AX and H3S10P) to paired cancer tissues. Profiling for the histone PTM changes in various other organs of normal and tumor bearing animal suggests that the changes in the histone PTMs observed in the tumor serum is indeed due to changes in the tumor tissue only. Further, we demonstrate that the observed hypo-acetylation of histone H4 in tissue and serum samples of tumor bearing animals corroborated with the elevated HDAC activity in both samples compared to normal. Interestingly, human normal and tumor serum samples also showed elevated HDAC activity with no significant changes in HAT activity. CONCLUSIONS: Our study provides the first evidence in the context of histone PTMs and modifiers that liquid biopsy is a valuable predictive tool for monitoring disease progression. Importantly, with the advent of drugs that target specific enzymes involved in the epigenetic regulation of gene expression, liquid biopsy-based ‘real time’ monitoring will be useful for subgrouping of the patients for epi-drug treatment, predicting response to therapy, early relapse and prognosis. BioMed Central 2017-03-29 /pmc/articles/PMC5372264/ /pubmed/28360947 http://dx.doi.org/10.1186/s13148-017-0330-x 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 | Methodology Reddy, Divya Khade, Bharat Pandya, Riddhi Gupta, Sanjay A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title | A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title_full | A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title_fullStr | A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title_full_unstemmed | A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title_short | A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
title_sort | novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours |
topic | Methodology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372264/ https://www.ncbi.nlm.nih.gov/pubmed/28360947 http://dx.doi.org/10.1186/s13148-017-0330-x |
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