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The prognostic capacities of CBP and p300 in locally advanced rectal cancer

BACKGROUND: CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorec...

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Autores principales: Rühlmann, Felix, Windhof-Jaidhauser, Indra Maria, Menze, Cornelius, Beißbarth, Tim, Bohnenberger, Hanibal, Ghadimi, Michael, Dango, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923994/
https://www.ncbi.nlm.nih.gov/pubmed/31856851
http://dx.doi.org/10.1186/s12957-019-1764-8
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author Rühlmann, Felix
Windhof-Jaidhauser, Indra Maria
Menze, Cornelius
Beißbarth, Tim
Bohnenberger, Hanibal
Ghadimi, Michael
Dango, Sebastian
author_facet Rühlmann, Felix
Windhof-Jaidhauser, Indra Maria
Menze, Cornelius
Beißbarth, Tim
Bohnenberger, Hanibal
Ghadimi, Michael
Dango, Sebastian
author_sort Rühlmann, Felix
collection PubMed
description BACKGROUND: CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment. METHODS: In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data. RESULTS: Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS; p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis. CONCLUSIONS: High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.
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spelling pubmed-69239942019-12-30 The prognostic capacities of CBP and p300 in locally advanced rectal cancer Rühlmann, Felix Windhof-Jaidhauser, Indra Maria Menze, Cornelius Beißbarth, Tim Bohnenberger, Hanibal Ghadimi, Michael Dango, Sebastian World J Surg Oncol Research BACKGROUND: CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment. METHODS: In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data. RESULTS: Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS; p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis. CONCLUSIONS: High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses. BioMed Central 2019-12-19 /pmc/articles/PMC6923994/ /pubmed/31856851 http://dx.doi.org/10.1186/s12957-019-1764-8 Text en © The Author(s). 2019 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
Rühlmann, Felix
Windhof-Jaidhauser, Indra Maria
Menze, Cornelius
Beißbarth, Tim
Bohnenberger, Hanibal
Ghadimi, Michael
Dango, Sebastian
The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title_full The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title_fullStr The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title_full_unstemmed The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title_short The prognostic capacities of CBP and p300 in locally advanced rectal cancer
title_sort prognostic capacities of cbp and p300 in locally advanced rectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923994/
https://www.ncbi.nlm.nih.gov/pubmed/31856851
http://dx.doi.org/10.1186/s12957-019-1764-8
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