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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

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

Authors: Monika Bauden, Theresa Kristl, Agata Sasor, Bodil Andersson, György Marko-Varga, Roland Andersson, Daniel Ansari

Published in: BMC Cancer | Issue 1/2017

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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 = 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.
Literature
1.
Malvezzi M, Carioli G, Bertuccio P, Rosso T, Boffetta P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol. 2016;27(4):725–31.CrossRefPubMed
2.
3.
Ansari D, Tingstedt B, Andersson B, Holmquist F, Sturesson C, Williamsson C, Sasor A, Borg D, Bauden M, Andersson R. Pancreatic cancer: yesterday, today and tomorrow. Future Oncol. 2016;12(16):1929–46.CrossRefPubMed
4.
Parikh AA, Maiga A, Bentrem D, Squires MH 3rd, Kooby DA, Maithel SK, Weber SM, Cho CS, Katz M, Martin RC, et al. Adjuvant therapy in pancreas cancer: does it influence patterns of recurrence? J Am Coll Surg. 2016;222(4):448–56.CrossRefPubMed
5.
Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52.CrossRefPubMed
6.
Guo M, Jia Y, Yu Z, House MG, Esteller M, Brock MV, Herman JG. Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas. Discov Med. 2014;17(92):67–73.PubMedPubMedCentral
7.
Omura N, Goggins M. Epigenetics and epigenetic alterations in pancreatic cancer. Int J Clin Exp Pathol. 2009;2(4):310–26.PubMed
8.
9.
Vardabasso C, Hasson D, Ratnakumar K, Chung CY, Duarte LF, Bernstein E. Histone variants: emerging players in cancer biology. Cell Mol Life Sci. 2014;71(3):379–404.CrossRefPubMed
10.
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 a resolution. Nature. 1997;389(6648):251–60.CrossRefPubMed
11.
Talbert PB, Henikoff S. Histone variants--ancient wrap artists of the epigenome. Nat Rev Mol Cell Biol. 2010;11(4):264–75.CrossRefPubMed
12.
Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15(11):703–8.CrossRefPubMed
13.
14.
Cheema MS, Ausio J. The structural determinants behind the epigenetic role of Histone variants. Genes (Basel). 2015;6(3):685–713.CrossRef
15.
Ferraro A. Altered primary chromatin structures and their implications in cancer development. Cell Oncol (Dordr). 2016;39(3):195–210.CrossRef
16.
Kwak HG, Dohmae N. Proteomic characterization of histone variants in the mouse testis by mass spectrometry-based top-down analysis. Biosci Trends. 2016;
17.
Bauden M, Kristl T, Andersson R, Marko-Varga G, Ansari D. Characterization of Histone-related PTMs and chemical modifications in FFPE and fresh frozen human pancreatic cancer Xenografts using LC-MS/MS. Lab Investig. 2017;97:279–88.CrossRefPubMed
18.
Giaginis C, Damaskos C, Koutsounas I, Zizi-Serbetzoglou A, Tsoukalas N, Patsouris E, Kouraklis G, Theocharis S. Histone deacetylase (HDAC)-1, −2, −4 and −6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival. BMC Gastroenterol. 2015;15:148.CrossRefPubMedPubMedCentral
19.
Boyne MT 2nd, Pesavento JJ, Mizzen CA, Kelleher NL. Precise characterization of human histones in the H2A gene family by top down mass spectrometry. J Proteome Res. 2006;5(2):248–53.CrossRefPubMed
20.
Happel N, Warneboldt J, Hanecke K, Haller F, Doenecke D. H1 subtype expression during cell proliferation and growth arrest. Cell Cycle. 2009;8(14):2226–32.CrossRefPubMed
21.
McBryant SJ, Lu X, Hansen JC. Multifunctionality of the linker histones: an emerging role for protein-protein interactions. Cell Res. 2010;20(5):519–28.CrossRefPubMedPubMedCentral
22.
Clausell J, Happel N, Hale TK, Doenecke D, Beato M. Histone H1 subtypes differentially modulate chromatin condensation without preventing ATP-dependent remodeling by SWI/SNF or NURF. PLoS One. 2009;4(10):e0007243.CrossRefPubMedPubMedCentral
23.
Rutowicz K, Puzio M, Halibart-Puzio J, Lirski M, Kotlinski M, Kroten MA, Knizewski L, Lange B, Muszewska A, Sniegowska-Swierk K, et al. A specialized Histone H1 variant is required for adaptive responses to complex Abiotic stress and related DNA Methylation in Arabidopsis. Plant Physiol. 2015;169(3):2080–101.PubMedPubMedCentral
24.
Yang SM, Kim BJ, Norwood Toro L, Skoultchi AI. H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation. Proc Natl Acad Sci U S A. 2013;110(5):1708–13.CrossRefPubMedPubMedCentral
25.
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;349(21):2042–54.CrossRefPubMed
26.
Tan AC, Jimeno A, Lin SH, Wheelhouse J, Chan F, Solomon A, Rajeshkumar NV, Rubio-Viqueira B, Hidalgo M. Characterizing DNA methylation patterns in pancreatic cancer genome. Mol Oncol. 2009;3(5–6):425–38.CrossRefPubMedPubMedCentral
27.
Herrera JE, West KL, Schiltz RL, Nakatani Y, Bustin M. Histone H1 is a specific repressor of core histone acetylation in chromatin. Mol Cell Biol. 2000;20(2):523–9.CrossRefPubMedPubMedCentral
28.
29.
Goru SK, Kadakol A, Pandey A, Malek V, Sharma N, Gaikwad AB. Histone H2AK119 and H2BK120 mono-ubiquitination modulate SET7/9 and SUV39H1 in type 1 diabetes-induced renal fibrosis. Biochem J. 2016;473(21):3937–49.CrossRefPubMed
30.
Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G, Hines OJ, Reber H, Seligson DB, Horvath S, et al. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J Clin Oncol. 2010;28(8):1358–65.CrossRefPubMedPubMedCentral
31.
Thompson MJ, Rubbi L, Dawson DW, Donahue TR, Pellegrini M. Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes. PLoS One. 2015;10(6):e0128814.CrossRefPubMedPubMedCentral
32.
33.
Hampton RY, Golenbock DT, Raetz CR, Lipid A. Binding sites in membranes of macrophage tumor cells. J Biol Chem. 1988;263(29):14802–7.PubMed
34.
Henriquez JP, Casar JC, Fuentealba L, Carey DJ, Brandan E. Extracellular matrix histone H1 binds to perlecan, is present in regenerating skeletal muscle and stimulates myoblast proliferation. J Cell Sci. 2002;115(Pt 10):2041–51.PubMed
35.
36.
Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM, DeClerck YA. Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res. 2012;72(10):2473–80.CrossRefPubMedPubMedCentral
Metadata
Title
Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma
Authors
Monika Bauden
Theresa Kristl
Agata Sasor
Bodil Andersson
György Marko-Varga
Roland Andersson
Daniel Ansari
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3834-z

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