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Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma

Bauden, Monika LU ; Kristl, Theresa LU ; Sasor, Agata; Andersson, Bodil LU ; Marko-Varga, György LU ; Andersson, Roland LU and Ansari, Daniel LU (2017) In BMC Cancer 17(1).
Abstract

Background: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: Histone variant H1.3 was found to be differentially expressed (p =... (More)

Background: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1-6.1), p = 0.029. Conclusion: We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Epigenetics, H1.3, Histone variants, Immunohistochemistry, LC-MS/MS, Pancreatic Ductal Adenocarcinoma
in
BMC Cancer
volume
17
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85036577918
  • wos:000416968100005
ISSN
1471-2407
DOI
10.1186/s12885-017-3834-z
language
English
LU publication?
yes
id
cdb308ee-ed14-4941-8943-4c6b912dafeb
date added to LUP
2017-12-18 08:51:01
date last changed
2018-01-16 13:27:59
@article{cdb308ee-ed14-4941-8943-4c6b912dafeb,
  abstract     = {<p>Background: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1-6.1), p = 0.029. Conclusion: We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.</p>},
  articleno    = {810},
  author       = {Bauden, Monika and Kristl, Theresa and Sasor, Agata and Andersson, Bodil and Marko-Varga, György and Andersson, Roland and Ansari, Daniel},
  issn         = {1471-2407},
  keyword      = {Biomarkers,Epigenetics,H1.3,Histone variants,Immunohistochemistry,LC-MS/MS,Pancreatic Ductal Adenocarcinoma},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma},
  url          = {http://dx.doi.org/10.1186/s12885-017-3834-z},
  volume       = {17},
  year         = {2017},
}