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Journal of Cancer Research and Clinical Oncology

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Open Access 01-08-2020 | Breast Cancer | Original Article – Cancer Research

Expression of H3K4me3 and H3K9ac in breast cancer

Authors: Luisa Berger, Thomas Kolben, Sarah Meister, Theresa M. Kolben, Elisa Schmoeckel, Doris Mayr, Sven Mahner, Udo Jeschke, Nina Ditsch, Susanne Beyer

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2020

Abstract

Purpose

Breast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survival

Methods

H3K4me3 and H3K9ac expression was immunohistochemically examined in 235 tissue samples.

Results

Positive estrogen receptor status was correlated with a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated to the Her2 status (p = 0.045) and to poor prognosis in cells with positive Ki67 status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated with a lower 10-year-survival (p = 0.026) and with lower breast cancer-specific survival (p = 0.004). High percentage score (> 190) of H3K9ac expression was correlated to worse breast cancer-specific survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023).

Conclusion

This analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated with survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.

Annunziato AT, Hansen JC (2000) Role of histone acetylation in the assembly and modulation of chromatin structures. Gene Expr 9:37–61. https://doi.org/10.3727/000000001783992687 CrossRefPubMed

Audia JE, Campbell RM (2016) Histone modifications and cancer. Cold Spring Harbor Perspect Biol 8:a019521. https://doi.org/10.1101/cshperspect.a019521 CrossRef

Bell R, Barraclough R, Vasieva O (2017) Gene expression meta-analysis of potential metastatic breast cancer markers. Curr Mol Med 17:200–210. https://doi.org/10.2174/1566524017666170807144946 CrossRefPubMedPubMedCentral

Beyer S et al (2017) Histone H3 acetyl K9 and histone H3 Tri methyl K4 as prognostic markers for patients with cervical cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18030477 CrossRefPubMedPubMedCentral

Cao Q-f, Qian S-b, Wang N, Zhang L, Wang W-m, Shen H-b (2015) TRPM2 mediates histone deacetylase inhibition-induced apoptosis in bladder cancer cells. Cancer Biother Radiopharm 30:87–93. https://doi.org/10.1089/cbr.2014.1697 CrossRefPubMed

DeSantis CE et al (2019) Breast cancer statistics, 2019. CA Cancer J Clin 69:438–451. https://doi.org/10.3322/caac.21583 CrossRefPubMed

Eckschlager T, Plch J, Stiborova M, Hrabeta J (2017) Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. https://doi.org/10.3390/ijms18071414 CrossRefPubMedPubMedCentral

Gao M et al (2016) Therapeutic potential and functional interaction of carfilzomib and vorinostat in T cell leukemia/lymphoma. Oncotarget 7:29102–29115. https://doi.org/10.18632/oncotarget.8667 CrossRefPubMedPubMedCentral

He C et al (2012) High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma. Hum Pathol 43:1425–1435. https://doi.org/10.1016/j.humpath.2011.11.003 CrossRefPubMed

Healey MA, Hu R, Beck AH, Collins LC, Schnitt SJ, Tamimi RM, Hazra A (2014) Association of H3K9me3 and H3K27me3 repressive histone marks with breast cancer subtypes in the Nurses' Health Study. Breast Cancer Res Treat 147:639–651. https://doi.org/10.1007/s10549-014-3089-1 CrossRefPubMed

Kimura H (2013) Histone modifications for human epigenome analysis. J Hum Genet 58:439. https://doi.org/10.1038/jhg.2013.66 CrossRefPubMed

Lawrence M, Daujat S, Schneider R (2016) Lateral thinking: how histone modifications regulate gene expression trends in genetics. TIG 32:42–56. https://doi.org/10.1016/j.tig.2015.10.007 CrossRefPubMed

Lee DY, Hayes JJ, Pruss D, Wolffe AP (1993) A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72:73–84. https://doi.org/10.1016/0092-8674(93)90051-q CrossRefPubMed

Leszinski G, Gezer U, Siegele B, Stoetzer O, Holdenrieder S (2012) Relevance of histone marks H3K9me3 and H4K20me3 in cancer. Anticancer Res 32:2199–2205PubMed

Li S, Shen L, Chen KN (2018) Association between H3K4 methylation and cancer prognosis: a meta-analysis. Thorac Cancer 9:794–799. https://doi.org/10.1111/1759-7714.12647 CrossRefPubMedPubMedCentral

Lima-Fernandes E, Murison A, da Silva Medina T et al (2019) Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells. Nat Commun 10(1):1436. https://doi.org/10.1038/s41467-019-09309-4 CrossRefPubMedPubMedCentral

Liu B-l et al (2010) Global Histone Modification Patterns as Prognostic Markers to Classify Glioma Patients Cancer. Epidemiol Biomark Prev 19:2888–2896. https://doi.org/10.1158/1055-9965.epi-10-0454 CrossRef

Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R (2007) FDA approval summary: vorinostat for treatment of advanced primary cutaneous T cell lymphoma. Oncologist 12:1247–1252. https://doi.org/10.1634/theoncologist.12-10-1247 CrossRefPubMed

Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84. https://doi.org/10.1038/nbt1272 CrossRefPubMed

Munster PN et al (2011) A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br J Cancer 104:1828–1835. https://doi.org/10.1038/bjc.2011.156 CrossRefPubMedPubMedCentral

Prat A et al (2015) Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast (Edinburgh, Scotland) 24(Suppl 2):S26–35. https://doi.org/10.1016/j.breast.2015.07.008 CrossRef

Rettig I et al (2015) Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation. Cell Death Dis 6:e1657. https://doi.org/10.1038/cddis.2015.24 CrossRefPubMedPubMedCentral

Ruthenburg AJ, Li H, Patel DJ, Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8:983–994. https://doi.org/10.1038/nrm2298 CrossRefPubMedPubMedCentral

Shanmugam MK et al (2018) Role of novel histone modifications in cancer. Oncotarget 9:11414–11426. https://doi.org/10.18632/oncotarget.23356 CrossRefPubMed

Shilatifard A (2008) Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 20:341–348. https://doi.org/10.1016/j.ceb.2008.03.019 CrossRefPubMedPubMedCentral

Takahashi YH, Shilatifard A (2010) Structural basis for H3K4 trimethylation by yeast Set1/COMPASS. Adv Enzyme Regul 50:104–110. https://doi.org/10.1016/j.advenzreg.2009.12.005 CrossRefPubMed

Terranova-Barberio M et al (2017) HDAC inhibition potentiates immunotherapy in triple negative breast cancer. Oncotarget 8:114156–114172. https://doi.org/10.18632/oncotarget.23169 CrossRefPubMedPubMedCentral

Thomas S, Thurn KT, Bicaku E, Marchion DC, Munster PN (2011) Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy. Breast Cancer Res Treat 130:437–447. https://doi.org/10.1007/s10549-011-1364-y CrossRefPubMedPubMedCentral

Torre LA, Islami F, Siegel RL, Ward EM, Jemal A (2017) Global cancer in women: burden and trends cancer. Epidemiol Biomark Prev 26:444–457. https://doi.org/10.1158/1055-9965.epi-16-0858 CrossRef

Vakoc CR, Sachdeva MM, Wang H, Blobel GA (2006) Profile of histone lysine methylation across transcribed mammalian chromatin. Mol Cell Biol 26:9185–9195. https://doi.org/10.1128/mcb.01529-06 CrossRefPubMedPubMedCentral

Wang Z et al (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897–903. https://doi.org/10.1038/ng.154 CrossRefPubMedPubMedCentral

Wu FR et al (2012) Differences in H3K4 trimethylation in in vivo and in vitro fertilization mouse preimplantation embryos. Genet Mol Res GMR 11:1099–1108. https://doi.org/10.4238/2012.April.27.9 CrossRefPubMed

Wu Y, Sarkissyan M, Vadgama JV (2015) Epigenetics in breast and prostate cancer. Methods Mol Biol (Clifton, NJ) 1238:425–466. https://doi.org/10.1007/978-1-4939-1804-1_23 CrossRef

Zhang P, Torres K, Liu X, Liu CG, Pollock RE (2016) An overview of chromatin-regulating proteins in cells. Curr Protein Peptide Sci 17:401–410. https://doi.org/10.2174/1389203717666160122120310 CrossRef

Zhang Q, Wang S, Chen J, Yu Z (2019) Histone deacetylases (HDACs) guided novel therapies for T cell lymphomas. Int J Med Sci 16:424–442. https://doi.org/10.7150/ijms.30154 CrossRefPubMedPubMedCentral

Title: Expression of H3K4me3 and H3K9ac in breast cancer
Authors: Luisa Berger
Thomas Kolben
Sarah Meister
Theresa M. Kolben
Elisa Schmoeckel
Doris Mayr
Sven Mahner
Udo Jeschke
Nina Ditsch
Susanne Beyer
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Epigenetics
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03265-z

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