{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:12:59Z","timestamp":1791987179557,"version":"4.4.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Faculty of Dentistry, Chulalongkorn University","award":["DRF 640008"],"award-info":[{"award-number":["DRF 640008"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Post-translational modification of histones is the crucial event that affect many tumor-specific traits. A diverse type of histone modifications had been reported in different cancers with prognostic implications. This study aimed to examine the degree of histone H3 modifications in salivary gland neoplasms and their associations with tumor pathologic characteristics and proliferative activity. The expression of H3K9Ac, H3K18Ac, H3K9Me3 and Ki-67 in 70 specimens of salivary gland neoplasms, consisting of 30 mucoepidermoid carcinoma (MEC), 20 adenoid cystic carcinoma (ACC) and 20 pleomorphic adenoma (PA), were investigated immunohistochemically. The immunohistochemical scoring of 3 histone modification types and Ki-67 labeling index were determined. Overall, MEC demonstrated elevated H3K9Ac level compared with benign PA. Increased H3K9Me3 in MEC was positively correlated with small nest invasion at tumor front, advanced pathologic grade, and elevated proliferative index. In addition, the significant upregulation of all 3 types of histone H3 modification was noted in solid subtype of ACC and associated with increased cell proliferation. This study indicates that salivary gland neoplasms differentially acquire distinct patterns of histone H3 modification, which impact prognostically relevant cancer phenotypes. The hyperacetylation and methylation of histone H3 could be underpinning the prognostically worsen solid type of ACC, and the trimethylation of H3K9 may be involved in aggressive characteristics of MEC.<\/jats:p>","DOI":"10.1038\/s41598-022-19174-9","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T10:15:10Z","timestamp":1662372910000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Distinct histone H3 modification profiles correlate with aggressive characteristics of salivary gland neoplasms"],"prefix":"10.1038","volume":"12","author":[{"given":"Aroonwan","family":"Lam-Ubol","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekarat","family":"Phattarataratip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"19174_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/2045-3701-4-45","volume":"4","author":"E Baxter","year":"2014","unstructured":"Baxter, E., Windloch, K., Gannon, F. & Lee, J. S. Epigenetic regulation in cancer progression. Cell Biosci. 4, 45. https:\/\/doi.org\/10.1186\/2045-3701-4-45 (2014).","journal-title":"Cell Biosci."},{"key":"19174_CR2","doi-asserted-by":"publisher","first-page":"4358","DOI":"10.1200\/JCO.2007.11.2599","volume":"25","author":"F Barlesi","year":"2007","unstructured":"Barlesi, F. et al. Global histone modifications predict prognosis of resected non small-cell lung cancer. J. Clin. Oncol. 25, 4358\u20134364. https:\/\/doi.org\/10.1200\/JCO.2007.11.2599 (2007).","journal-title":"J. Clin. Oncol."},{"key":"19174_CR3","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1186\/s12885-017-3853-9","volume":"17","author":"S Damodaran","year":"2017","unstructured":"Damodaran, S. et al. Dysregulation of Sirtuin 2 (SIRT2) and histone H3K18 acetylation pathways associates with adverse prostate cancer outcomes. BMC Cancer 17, 874. https:\/\/doi.org\/10.1186\/s12885-017-3853-9 (2017).","journal-title":"BMC Cancer"},{"key":"19174_CR4","doi-asserted-by":"publisher","first-page":"3802","DOI":"10.1158\/0008-5472.CAN-08-3907","volume":"69","author":"SE Elsheikh","year":"2009","unstructured":"Elsheikh, S. E. et al. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 69, 3802\u20133809. https:\/\/doi.org\/10.1158\/0008-5472.CAN-08-3907 (2009).","journal-title":"Cancer Res."},{"key":"19174_CR5","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s13277-012-0554-5","volume":"34","author":"U Gezer","year":"2013","unstructured":"Gezer, U. et al. Characterization of H3K9me3- and H4K20me3-associated circulating nucleosomal DNA by high-throughput sequencing in colorectal cancer. Tumour Biol 34, 329\u2013336. https:\/\/doi.org\/10.1007\/s13277-012-0554-5 (2013).","journal-title":"Tumour Biol"},{"key":"19174_CR6","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1097\/PAI.0000000000000194","volume":"24","author":"CN Juliano","year":"2016","unstructured":"Juliano, C. N. et al. H4K12 and H3K18 acetylation associates with poor prognosis in pancreatic cancer. Appl. Immunohistochem. Mol. Morpho. 24, 337\u2013344. https:\/\/doi.org\/10.1097\/PAI.0000000000000194 (2016).","journal-title":"Appl. Immunohistochem. Mol. Morpho."},{"key":"19174_CR7","first-page":"2199","volume":"32","author":"G Leszinski","year":"2012","unstructured":"Leszinski, G., Gezer, U., Siegele, B., Stoetzer, O. & Holdenrieder, S. Relevance of histone marks H3K9me3 and H4K20me3 in cancer. Anticancer Res. 32, 2199\u20132205 (2012).","journal-title":"Anticancer Res."},{"key":"19174_CR8","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1200\/JCO.2009.24.5639","volume":"28","author":"A Manuyakorn","year":"2010","unstructured":"Manuyakorn, A. et al. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: Results from RTOG 9704. J. Clin. Oncol. 28, 1358\u20131365. https:\/\/doi.org\/10.1200\/JCO.2009.24.5639 (2010).","journal-title":"J. Clin. Oncol."},{"key":"19174_CR9","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1111\/j.1349-7006.2010.01717.x","volume":"101","author":"D Mosashvilli","year":"2010","unstructured":"Mosashvilli, D. et al. Global histone acetylation levels: Prognostic relevance in patients with renal cell carcinoma. Cancer Sci. 101, 2664\u20132669. https:\/\/doi.org\/10.1111\/j.1349-7006.2010.01717.x (2010).","journal-title":"Cancer Sci."},{"key":"19174_CR10","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1245\/s10434-008-9927-9","volume":"15","author":"YS Park","year":"2008","unstructured":"Park, Y. S. et al. The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann. Surg. Oncol. 15, 1968\u20131976. https:\/\/doi.org\/10.1245\/s10434-008-9927-9 (2008).","journal-title":"Ann. Surg. Oncol."},{"key":"19174_CR11","doi-asserted-by":"publisher","first-page":"13726","DOI":"10.1002\/jcb.28645","volume":"120","author":"P Paydar","year":"2019","unstructured":"Paydar, P. et al. Epigenetic modulation of BRCA-1 and MGMT genes, and histones H4 and H3 are associated with breast tumors. J. Cell Biochem. 120, 13726\u201313736. https:\/\/doi.org\/10.1002\/jcb.28645 (2019).","journal-title":"J. Cell Biochem."},{"key":"19174_CR12","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1038\/nature03672","volume":"435","author":"DB Seligson","year":"2005","unstructured":"Seligson, D. B. et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435, 1262\u20131266. https:\/\/doi.org\/10.1038\/nature03672 (2005).","journal-title":"Nature"},{"key":"19174_CR13","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1111\/j.1440-1827.2011.02776.x","volume":"62","author":"JS Song","year":"2012","unstructured":"Song, J. S., Kim, Y. S., Kim, D. K., Park, S. I. & Jang, S. J. Global histone modification pattern associated with recurrence and disease-free survival in non-small cell lung cancer patients. Pathol. Int. 62, 182\u2013190. https:\/\/doi.org\/10.1111\/j.1440-1827.2011.02776.x (2012).","journal-title":"Pathol. Int."},{"key":"19174_CR14","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/modpathol.2008.172","volume":"22","author":"C Tzao","year":"2009","unstructured":"Tzao, C. et al. Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus. Mod. Pathol. 22, 252\u2013260. https:\/\/doi.org\/10.1038\/modpathol.2008.172 (2009).","journal-title":"Mod. Pathol."},{"key":"19174_CR15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.4161\/epi.6.1.13331","volume":"6","author":"JC Black","year":"2011","unstructured":"Black, J. C. & Whetstine, J. R. Chromatin landscape: Methylation beyond transcription. Epigenetics 6, 9\u201315. https:\/\/doi.org\/10.4161\/epi.6.1.13331 (2011).","journal-title":"Epigenetics"},{"key":"19174_CR16","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","volume":"129","author":"A Barski","year":"2007","unstructured":"Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823\u2013837. https:\/\/doi.org\/10.1016\/j.cell.2007.05.009 (2007).","journal-title":"Cell"},{"key":"19174_CR17","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13046-020-01682-z","volume":"39","author":"C Yang","year":"2020","unstructured":"Yang, C. et al. Histone methyltransferase and drug resistance in cancers. J. Exp. Clin. Cancer Res. 39, 173. https:\/\/doi.org\/10.1186\/s13046-020-01682-z (2020).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"19174_CR18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41392-019-0095-0","volume":"4","author":"Y Cheng","year":"2019","unstructured":"Cheng, Y. et al. Targeting epigenetic regulators for cancer therapy: Mechanisms and advances in clinical trials. Signal Transduct. Target Ther. 4, 62. https:\/\/doi.org\/10.1038\/s41392-019-0095-0 (2019).","journal-title":"Signal Transduct. Target Ther."},{"key":"19174_CR19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13148-019-0644-y","volume":"11","author":"J Torrano","year":"2019","unstructured":"Torrano, J., Al Emran, A., Hammerlindl, H. & Schaider, H. Emerging roles of H3K9me3, SETDB1 and SETDB2 in therapy-induced cellular reprogramming. Clin. Epigenetics 11, 43. https:\/\/doi.org\/10.1186\/s13148-019-0644-y (2019).","journal-title":"Clin. Epigenetics"},{"key":"19174_CR20","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1111\/cas.12166","volume":"104","author":"Y Yokoyama","year":"2013","unstructured":"Yokoyama, Y. et al. Cancer-associated upregulation of histone H3 lysine 9 trimethylation promotes cell motility in vitro and drives tumor formation in vivo. Cancer Sci. 104, 889\u2013895. https:\/\/doi.org\/10.1111\/cas.12166 (2013).","journal-title":"Cancer Sci."},{"key":"19174_CR21","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1158\/1055-9965.EPI-10-0555","volume":"19","author":"T Bianco-Miotto","year":"2010","unstructured":"Bianco-Miotto, T. et al. Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol. Biomarkers Prev. 19, 2611\u20132622. https:\/\/doi.org\/10.1158\/1055-9965.EPI-10-0555 (2010).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"19174_CR22","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1111\/jop.12557","volume":"46","author":"VP Wagner","year":"2017","unstructured":"Wagner, V. P. et al. Reduced chromatin acetylation of malignant salivary gland tumors correlates with enhanced proliferation. J. Oral Pathol. Med. 46, 792\u2013797. https:\/\/doi.org\/10.1111\/jop.12557 (2017).","journal-title":"J. Oral Pathol. Med."},{"key":"19174_CR23","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.5858\/arpa.2012-0704-OA","volume":"137","author":"R Xia","year":"2013","unstructured":"Xia, R. et al. High expression of H3K9me3 is a strong predictor of poor survival in patients with salivary adenoid cystic carcinoma. Arch. Pathol. Lab. Med. 137, 1761\u20131769. https:\/\/doi.org\/10.5858\/arpa.2012-0704-OA (2013).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"19174_CR24","first-page":"2063","volume":"26","author":"F Aniello","year":"2006","unstructured":"Aniello, F. et al. Expression of four histone lysine-methyltransferases in parotid gland tumors. Anticancer Res. 26, 2063\u20132067 (2006).","journal-title":"Anticancer Res."},{"key":"19174_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11030517","author":"D Pouloudi","year":"2021","unstructured":"Pouloudi, D. et al. Clinical significance of histone deacetylase (HDAC)-1, -2, -4 and -6 expression in salivary gland tumors. Diagnostics. https:\/\/doi.org\/10.3390\/diagnostics11030517 (2021).","journal-title":"Diagnostics."},{"key":"19174_CR26","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1097\/00000478-200107000-00001","volume":"25","author":"MS Brandwein","year":"2001","unstructured":"Brandwein, M. S. et al. Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading. Am. J. Surg. Pathol. 25, 835\u2013845. https:\/\/doi.org\/10.1097\/00000478-200107000-00001 (2001).","journal-title":"Am. J. Surg. Pathol."},{"key":"19174_CR27","first-page":"716","volume":"109","author":"KS McCarty Jr","year":"1985","unstructured":"McCarty, K. S. Jr., Miller, L. S., Cox, E. B., Konrath, J. & McCarty, K. S. Sr. Estrogen receptor analyses: Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch. Pathol. Lab. Med. 109, 716\u2013721 (1985).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"19174_CR28","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/j.1600-0714.2012.01148.x","volume":"41","author":"SR Larsen","year":"2012","unstructured":"Larsen, S. R., Bjorndal, K., Godballe, C. & Krogdahl, A. Prognostic significance of Ki-67 in salivary gland carcinomas. J. Oral. Pathol. Med. 41, 598\u2013602. https:\/\/doi.org\/10.1111\/j.1600-0714.2012.01148.x (2012).","journal-title":"J. Oral. Pathol. Med."},{"key":"19174_CR29","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1038\/sj.onc.1210895","volume":"27","author":"JK Wiencke","year":"2008","unstructured":"Wiencke, J. K., Zheng, S., Morrison, Z. & Yeh, R. F. Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells. Oncogene 27, 2412\u20132421. https:\/\/doi.org\/10.1038\/sj.onc.1210895 (2008).","journal-title":"Oncogene"},{"key":"19174_CR30","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3389\/fonc.2019.00705","volume":"9","author":"L Monaghan","year":"2019","unstructured":"Monaghan, L. et al. The emerging role of H3K9me3 as a potential therapeutic target in acute myeloid leukemia. Front Oncol. 9, 705. https:\/\/doi.org\/10.3389\/fonc.2019.00705 (2019).","journal-title":"Front Oncol."},{"key":"19174_CR31","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12885-018-4061-y","volume":"18","author":"C Lu","year":"2018","unstructured":"Lu, C. et al. Contrasting roles of H3K4me3 and H3K9me3 in regulation of apoptosis and gemcitabine resistance in human pancreatic cancer cells. BMC Cancer 18, 149. https:\/\/doi.org\/10.1186\/s12885-018-4061-y (2018).","journal-title":"BMC Cancer"},{"key":"19174_CR32","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1007\/s10620-019-05529-2","volume":"64","author":"M Zhou","year":"2019","unstructured":"Zhou, M. et al. H3K9me3, H3K36me3, and H4K20me3 expression correlates with patient outcome in esophageal squamous cell carcinoma as epigenetic markers. Dig. Dis. Sci. 64, 2147\u20132157. https:\/\/doi.org\/10.1007\/s10620-019-05529-2 (2019).","journal-title":"Dig. Dis. Sci."},{"key":"19174_CR33","doi-asserted-by":"publisher","first-page":"8651","DOI":"10.1038\/ncomms9651","volume":"6","author":"Q Fei","year":"2015","unstructured":"Fei, Q. et al. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53. Nat. Commun. 6, 8651. https:\/\/doi.org\/10.1038\/ncomms9651 (2015).","journal-title":"Nat. Commun."},{"key":"19174_CR34","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nature09806","volume":"471","author":"CJ Ceol","year":"2011","unstructured":"Ceol, C. J. et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature 471, 513\u2013517. https:\/\/doi.org\/10.1038\/nature09806 (2011).","journal-title":"Nature"},{"key":"19174_CR35","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1172\/JCI77976","volume":"125","author":"EZ Keung","year":"2015","unstructured":"Keung, E. Z. et al. Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma. J. Clin. Invest. 125, 2965\u20132978. https:\/\/doi.org\/10.1172\/JCI77976 (2015).","journal-title":"J. Clin. Invest."},{"key":"19174_CR36","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/onc.2009.361","volume":"29","author":"A Lakshmikuttyamma","year":"2010","unstructured":"Lakshmikuttyamma, A., Scott, S. A., DeCoteau, J. F. & Geyer, C. R. Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition. Oncogene 29, 576\u2013588. https:\/\/doi.org\/10.1038\/onc.2009.361 (2010).","journal-title":"Oncogene"},{"key":"19174_CR37","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.4049\/jimmunol.1402243","volume":"195","author":"AV Paschall","year":"2015","unstructured":"Paschall, A. V. et al. H3K9 trimethylation silences fas expression to confer colon carcinoma immune escape and 5-fluorouracil chemoresistance. J. Immunol. 195, 1868\u20131882. https:\/\/doi.org\/10.4049\/jimmunol.1402243 (2015).","journal-title":"J. Immunol."},{"key":"19174_CR38","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1002\/path.4482","volume":"235","author":"QY Sun","year":"2015","unstructured":"Sun, Q. Y. et al. SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway. J. Pathol. 235, 559\u2013570. https:\/\/doi.org\/10.1002\/path.4482 (2015).","journal-title":"J. Pathol."},{"key":"19174_CR39","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40659-018-0189-0","volume":"51","author":"M Wu","year":"2018","unstructured":"Wu, M. et al. Knockdown of SETDB1 inhibits breast cancer progression by miR-381-3p-related regulation. Biol. Res. 51, 39. https:\/\/doi.org\/10.1186\/s40659-018-0189-0 (2018).","journal-title":"Biol. Res."},{"key":"19174_CR40","doi-asserted-by":"publisher","first-page":"319","DOI":"10.4103\/1008-682X.122812","volume":"16","author":"Y Sun","year":"2014","unstructured":"Sun, Y. et al. Histone methyltransferase SETDB1 is required for prostate cancer cell proliferation, migration and invasion. Asian J. Androl. 16, 319\u2013324. https:\/\/doi.org\/10.4103\/1008-682X.122812 (2014).","journal-title":"Asian J. Androl."},{"key":"19174_CR41","doi-asserted-by":"publisher","first-page":"7830","DOI":"10.1158\/0008-5472.CAN-10-0833","volume":"70","author":"MW Chen","year":"2010","unstructured":"Chen, M. W. et al. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res. 70, 7830\u20137840. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-0833 (2010).","journal-title":"Cancer Res."},{"key":"19174_CR42","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.anndiagpath.2016.05.007","volume":"24","author":"E Phattarataratip","year":"2016","unstructured":"Phattarataratip, E., Masorn, M., Jarupoonphol, W., Supatthanayut, S. & Saeoweiang, P. Differential expression of epithelial cell adhesion molecule in salivary gland neoplasms. Ann. Diagn. Pathol. 24, 62\u201367. https:\/\/doi.org\/10.1016\/j.anndiagpath.2016.05.007 (2016).","journal-title":"Ann. Diagn. Pathol."},{"key":"19174_CR43","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1002\/cncr.29890","volume":"122","author":"LX Yin","year":"2016","unstructured":"Yin, L. X. & Ha, P. K. Genetic alterations in salivary gland cancers. Cancer 122, 1822\u20131831. https:\/\/doi.org\/10.1002\/cncr.29890 (2016).","journal-title":"Cancer"},{"key":"19174_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091034","author":"AA Igolkina","year":"2019","unstructured":"Igolkina, A. A. et al. H3K4me3, H3K9ac, H3K27ac, H3K27me3 and H3K9me3 histone tags suggest distinct regulatory evolution of open and condensed chromatin landmarks. Cells https:\/\/doi.org\/10.3390\/cells8091034 (2019).","journal-title":"Cells"},{"key":"19174_CR45","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/his.13218","volume":"71","author":"LP Webber","year":"2017","unstructured":"Webber, L. P. et al. Hypoacetylation of acetyl-histone H3 (H3K9ac) as marker of poor prognosis in oral cancer. Histopathology 71, 278\u2013286. https:\/\/doi.org\/10.1111\/his.13218 (2017).","journal-title":"Histopathology"},{"key":"19174_CR46","first-page":"664","volume":"6","author":"L Lutz","year":"2016","unstructured":"Lutz, L. et al. Histone modifiers and marks define heterogeneous groups of colorectal carcinomas and affect responses to HDAC inhibitors in vitro. Am. J. Cancer Res. 6, 664\u2013676 (2016).","journal-title":"Am. J. Cancer Res."},{"key":"19174_CR47","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.bbrc.2011.06.182","volume":"411","author":"C Puppin","year":"2011","unstructured":"Puppin, C. et al. Levels of histone acetylation in thyroid tumors. Biochem. Biophys. Res. Commun. 411, 679\u2013683. https:\/\/doi.org\/10.1016\/j.bbrc.2011.06.182 (2011).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"19174_CR48","doi-asserted-by":"publisher","first-page":"2888","DOI":"10.1158\/1055-9965.EPI-10-0454","volume":"19","author":"BL Liu","year":"2010","unstructured":"Liu, B. L. et al. Global histone modification patterns as prognostic markers to classify glioma patients. Cancer Epidemiol. Biomarkers Prev. 19, 2888\u20132896. https:\/\/doi.org\/10.1158\/1055-9965.EPI-10-0454 (2010).","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"19174_CR49","doi-asserted-by":"publisher","first-page":"337","DOI":"10.4132\/jptm.2016.05.20","volume":"50","author":"HS Lee","year":"2016","unstructured":"Lee, H. S. et al. SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma. J. Pathol. Transl. Med. 50, 337\u2013344. https:\/\/doi.org\/10.4132\/jptm.2016.05.20 (2016).","journal-title":"J. Pathol. Transl. Med."},{"key":"19174_CR50","doi-asserted-by":"publisher","first-page":"4259","DOI":"10.1002\/cncr.28356","volume":"119","author":"YW Chen","year":"2013","unstructured":"Chen, Y. W., Kao, S. Y., Wang, H. J. & Yang, M. H. Histone modification patterns correlate with patient outcome in oral squamous cell carcinoma. Cancer 119, 4259\u20134267. https:\/\/doi.org\/10.1002\/cncr.28356 (2013).","journal-title":"Cancer"},{"key":"19174_CR51","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1007\/s10620-008-0601-7","volume":"54","author":"H Ashktorab","year":"2009","unstructured":"Ashktorab, H. et al. Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig. Dis. Sci. 54, 2109\u20132117. https:\/\/doi.org\/10.1007\/s10620-008-0601-7 (2009).","journal-title":"Dig. Dis. Sci."},{"key":"19174_CR52","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1158\/0008-5472.CAN-18-3767","volume":"79","author":"H Ji","year":"2019","unstructured":"Ji, H. et al. HDAC3 deficiency promotes liver cancer through a defect in H3K9ac\/H3K9me3 transition. Cancer Res. 79, 3676\u20133688. https:\/\/doi.org\/10.1158\/0008-5472.CAN-18-3767 (2019).","journal-title":"Cancer Res."},{"key":"19174_CR53","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1177\/039463201302600210","volume":"26","author":"ZL Cui","year":"2013","unstructured":"Cui, Z. L. et al. Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats. Int. J. Immunopathol. Pharmacol. 26, 371\u2013381. https:\/\/doi.org\/10.1177\/039463201302600210 (2013).","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"19174_CR54","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41392-020-00388-0","volume":"6","author":"W Ni","year":"2021","unstructured":"Ni, W. et al. Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma. Signal Transduct. Target Ther. 6, 27. https:\/\/doi.org\/10.1038\/s41392-020-00388-0 (2021).","journal-title":"Signal Transduct. Target Ther."},{"key":"19174_CR55","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1158\/0008-5472.CAN-07-6844","volume":"68","author":"N Yamada","year":"2008","unstructured":"Yamada, N. et al. MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells. Cancer Res. 68, 2708\u20132716. https:\/\/doi.org\/10.1158\/0008-5472.CAN-07-6844 (2008).","journal-title":"Cancer Res."},{"key":"19174_CR56","doi-asserted-by":"publisher","first-page":"10524","DOI":"10.1128\/JVI.01077-12","volume":"86","author":"J Zhang","year":"2012","unstructured":"Zhang, J., Markus, J., Bies, J., Paul, T. & Wolff, L. Three murine leukemia virus integration regions within 100 kilobases upstream of c-myb are proximal to the 5\u2019 regulatory region of the gene through DNA looping. J. Virol. 86, 10524\u201310532. https:\/\/doi.org\/10.1128\/JVI.01077-12 (2012).","journal-title":"J. Virol."},{"key":"19174_CR57","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/sj.bjc.6605788","volume":"103","author":"B Lujan","year":"2010","unstructured":"Lujan, B. et al. Activation of the EGFR\/ERK pathway in high-grade mucoepidermoid carcinomas of the salivary glands. Br. J. Cancer 103, 510\u2013516. https:\/\/doi.org\/10.1038\/sj.bjc.6605788 (2010).","journal-title":"Br. J. Cancer"},{"key":"19174_CR58","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14040992","author":"LE Miller","year":"2022","unstructured":"Miller, L. E. et al. A contemporary review of molecular therapeutic targets for adenoid cystic carcinoma. Cancers https:\/\/doi.org\/10.3390\/cancers14040992 (2022).","journal-title":"Cancers"},{"key":"19174_CR59","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12920-019-0477-8","volume":"12","author":"M Nava","year":"2019","unstructured":"Nava, M. et al. Transcriptomic and ChIP-sequence interrogation of EGFR signaling in HER2+ breast cancer cells reveals a dynamic chromatin landscape and S100 genes as targets. BMC Med. Genomics 12, 32. https:\/\/doi.org\/10.1186\/s12920-019-0477-8 (2019).","journal-title":"BMC Med. Genomics"},{"key":"19174_CR60","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s12105-013-0432-5","volume":"7","author":"D Bell","year":"2013","unstructured":"Bell, D. & El-Naggar, A. K. Molecular heterogeneity in mucoepidermoid carcinoma: Conceptual and practical implications. Head Neck Pathol. 7, 23\u201327. https:\/\/doi.org\/10.1007\/s12105-013-0432-5 (2013).","journal-title":"Head Neck Pathol."},{"key":"19174_CR61","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/emboj.2010.318","volume":"30","author":"Q Jin","year":"2011","unstructured":"Jin, Q. et al. Distinct roles of GCN5\/PCAF-mediated H3K9ac and CBP\/p300-mediated H3K18\/27ac in nuclear receptor transactivation. EMBO J. 30, 249\u2013262. https:\/\/doi.org\/10.1038\/emboj.2010.318 (2011).","journal-title":"EMBO J."},{"key":"19174_CR62","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1038\/sj.emboj.7600719","volume":"24","author":"L Wu","year":"2005","unstructured":"Wu, L. et al. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. EMBO J. 24, 2391\u20132402. https:\/\/doi.org\/10.1038\/sj.emboj.7600719 (2005).","journal-title":"EMBO J."},{"key":"19174_CR63","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.oraloncology.2004.08.004","volume":"41","author":"M Kishi","year":"2005","unstructured":"Kishi, M. et al. Genetic and epigenetic alteration profiles for multiple genes in salivary gland carcinomas. Oral Oncol. 41, 161\u2013169. https:\/\/doi.org\/10.1016\/j.oraloncology.2004.08.004 (2005).","journal-title":"Oral Oncol."},{"key":"19174_CR64","doi-asserted-by":"publisher","first-page":"5630","DOI":"10.1200\/JCO.2008.17.3567","volume":"26","author":"RL Camp","year":"2008","unstructured":"Camp, R. L., Neumeister, V. & Rimm, D. L. A decade of tissue microarrays: Progress in the discovery and validation of cancer biomarkers. J. Clin. Oncol. 26, 5630\u20135637. https:\/\/doi.org\/10.1200\/JCO.2008.17.3567 (2008).","journal-title":"J. Clin. Oncol."},{"key":"19174_CR65","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/jnc.14849","volume":"152","author":"Z Huang","year":"2020","unstructured":"Huang, Z. et al. Histone deacetylase 6 promotes growth of glioblastoma through the MKK7\/JNK\/c-Jun signaling pathway. J. Neurochem. 152, 221\u2013234. https:\/\/doi.org\/10.1111\/jnc.14849 (2020).","journal-title":"J. Neurochem."},{"key":"19174_CR66","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3389\/fnmol.2017.00376","volume":"10","author":"Q Lai","year":"2017","unstructured":"Lai, Q. et al. H3K9ac and HDAC2 activity are involved in the expression of monocarboxylate transporter 1 in oligodendrocyte. Front Mol. Neurosci. 10, 376. https:\/\/doi.org\/10.3389\/fnmol.2017.00376 (2017).","journal-title":"Front Mol. Neurosci."},{"key":"19174_CR67","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2337\/db11-0313","volume":"61","author":"R Winkler","year":"2012","unstructured":"Winkler, R. et al. Histone deacetylase 6 (HDAC6) is an essential modifier of glucocorticoid-induced hepatic gluconeogenesis. Diabetes 61, 513\u2013523. https:\/\/doi.org\/10.2337\/db11-0313 (2012).","journal-title":"Diabetes"},{"key":"19174_CR68","doi-asserted-by":"publisher","first-page":"14690","DOI":"10.1038\/s41598-018-32927-9","volume":"8","author":"RDW Kelly","year":"2018","unstructured":"Kelly, R. D. W. et al. Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo. Sci. Rep. 8, 14690. https:\/\/doi.org\/10.1038\/s41598-018-32927-9 (2018).","journal-title":"Sci. Rep."},{"key":"19174_CR69","doi-asserted-by":"publisher","first-page":"196","DOI":"10.2174\/157488410791498770","volume":"5","author":"JH Beumer","year":"2010","unstructured":"Beumer, J. H. & Tawbi, H. Role of histone deacetylases and their inhibitors in cancer biology and treatment. Curr. Clin. Pharmacol. 5, 196\u2013208. https:\/\/doi.org\/10.2174\/157488410791498770 (2010).","journal-title":"Curr. Clin. Pharmacol."},{"key":"19174_CR70","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1093\/bib\/bbt060","volume":"15","author":"T Li","year":"2014","unstructured":"Li, T., Song, B., Wu, Z., Lu, M. & Zhu, W. G. Systematic identification of Class I HDAC substrates. Brief Bioinform. 15, 963\u2013972. https:\/\/doi.org\/10.1093\/bib\/bbt060 (2014).","journal-title":"Brief Bioinform."},{"key":"19174_CR71","doi-asserted-by":"publisher","DOI":"10.3390\/genes11050556","author":"G Milazzo","year":"2020","unstructured":"Milazzo, G. et al. Histone deacetylases (HDACs): Evolution, specificity, role in transcriptional complexes, and pharmacological actionability. Genes https:\/\/doi.org\/10.3390\/genes11050556 (2020).","journal-title":"Genes"},{"key":"19174_CR72","doi-asserted-by":"publisher","first-page":"32918","DOI":"10.18632\/oncotarget.16464","volume":"8","author":"PH Goncalves","year":"2017","unstructured":"Goncalves, P. H. et al. A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma. Oncotarget 8, 32918\u201332929. https:\/\/doi.org\/10.18632\/oncotarget.16464 (2017).","journal-title":"Oncotarget"},{"key":"19174_CR73","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1158\/1078-0432.CCR-19-2214","volume":"26","author":"CP Rodriguez","year":"2020","unstructured":"Rodriguez, C. P. et al. A phase II trial of pembrolizumab and vorinostat in recurrent metastatic head and neck squamous cell carcinomas and salivary gland cancer. Clin. Cancer Res. 26, 837\u2013845. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-2214 (2020).","journal-title":"Clin. Cancer Res."},{"key":"19174_CR74","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1038\/s41598-018-20345-w","volume":"8","author":"VP Wagner","year":"2018","unstructured":"Wagner, V. P. et al. Targeting histone deacetylase and NFkappaB signaling as a novel therapy for Mucoepidermoid Carcinomas. Sci. Rep. 8, 2065. https:\/\/doi.org\/10.1038\/s41598-018-20345-w (2018).","journal-title":"Sci. Rep."},{"key":"19174_CR75","doi-asserted-by":"publisher","first-page":"3629","DOI":"10.1093\/nar\/gkv1504","volume":"44","author":"PY Zhang","year":"2016","unstructured":"Zhang, P. Y. et al. Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents. Nucleic Acids Res. 44, 3629\u20133642. https:\/\/doi.org\/10.1093\/nar\/gkv1504 (2016).","journal-title":"Nucleic Acids Res."},{"key":"19174_CR76","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1111\/odi.13253","volume":"26","author":"ES Dos Santos","year":"2020","unstructured":"Dos Santos, E. S., Ramos, J. C., Normando, A. G. C., Mariano, F. V. & Paes Leme, A. F. Epigenetic alterations in salivary gland tumors. Oral Dis. 26, 1610\u20131618. https:\/\/doi.org\/10.1111\/odi.13253 (2020).","journal-title":"Oral Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19174-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19174-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19174-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T10:21:03Z","timestamp":1662373263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19174-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,5]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["19174"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-19174-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,5]]},"assertion":[{"value":"15 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15063"}}