{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:29:51Z","timestamp":1791876591822,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Recent advances demonstrate the role of chromatin regulators, including histone variants and histone chaperones, in cancer initiation and progression. Methods: Histone H3K4me3, histone variant centromere protein (CENP-A) and histone chaperones Holliday junction recognition protein (HJURP) as well as DAXX expression were examined immunohistochemically in 95 thymic epithelial tumor (TET) specimens. Our results were compared with the expression profile of DAXX, HJURP and CENP-A in gene expression profiling interactive analysis (GEPIA2). Results: The lymphocyte-poor B3- and C-type TETs were more frequently DAXX negative (p = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (p = 0.007 and p = 0.002) and higher cytoplasmic HJURP H-score (p &lt; 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka\u2013Koga stage (p = 0.048 and p &lt; 0.001). A positive correlation between HJURP and CENP-A was also observed. The presence of cytoplasmic CENP-A expression was correlated with a favorable overall survival (p = 0.03). CENP-A overexpression in survival analysis of TCGA TETs showed similar results. H3K4me3 expression was not associated with any clinicopathological parameters. Conclusions: Our results suggest a significant interaction between CENP-A and HJURP in TETs. Moreover, we confirmed the presence of a cytoplasmic CENP-A immunolocalization, suggesting also a possible favorable prognostic value of this specific immunostaining pattern.<\/jats:p>","DOI":"10.3390\/ijms23158339","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4728-7104","authenticated-orcid":false,"given":"Georgia","family":"Levidou","sequence":"first","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Pathology, Paracelsus Medical University, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Palamaris","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros G.","family":"Sykaras","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Andreadakis","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-7046","authenticated-orcid":false,"given":"Christos","family":"Masaoutis","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-3528","authenticated-orcid":false,"given":"Irene","family":"Theochari","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Korkolopoulou","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Rontogianni","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatios","family":"Theocharis","sequence":"additional","affiliation":[{"name":"First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nrc3130","article-title":"A decade of exploring the cancer epigenome\u2014Biological and translational implications","volume":"11","author":"Baylin","year":"2011","journal-title":"Nat. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101900","DOI":"10.1016\/j.gde.2022.101900","article-title":"H3-H4 Histone Chaperones and Cancer","volume":"73","author":"Almouzni","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.molonc.2014.11.002","article-title":"The Histone Chaperone HJURP Is a New Independent Prognostic Marker for Luminal A Breast Carcinoma","volume":"9","author":"Berger","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1756-8935-6-24","article-title":"Proteomic Characterization of Novel Histone Post-Translational Modifications","volume":"6","author":"Arnaudo","year":"2013","journal-title":"Epigenet. Chromatin"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ng.154","article-title":"Combinatorial Patterns of Histone Acetylations and Methylations in the Human Genome","volume":"40","author":"Wang","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.15252\/embr.201540945","article-title":"The Interplay of Histone Modifications-Writers That Read","volume":"16","author":"Zhang","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/266273a0","article-title":"Non-Allelic Variants of Histones 2a, 2b and 3 in Mammals","volume":"266","author":"Franklin","year":"1977","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/nsb996","article-title":"Phylogenomics of the Nucleosome","volume":"10","author":"Malik","year":"2003","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0092-8674(89)90398-X","article-title":"Purification and Characterization of CAF-I, a Human Cell Factor Required for Chromatin Assembly during DNA Replication in Vitro","volume":"58","author":"Smith","year":"1989","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrg.2016.157","article-title":"Chromatin Dynamics during the Cell Cycle at Centromeres","volume":"18","author":"Almouzni","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-981-15-8104-5_2","article-title":"The Histone H3 Family and Its Deposition Pathways","volume":"1283","author":"Almouzni","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.02.040","article-title":"HJURP Is a Cell-Cycle-Dependent Maintenance and Deposition Factor of CENP-A at Centromeres","volume":"137","author":"Dunleavy","year":"2009","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cell.2009.02.039","article-title":"Centromere-Specific Assembly of CENP-a Nucleosomes Is Mediated by HJURP","volume":"137","author":"Foltz","year":"2009","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/sqb.2017.82.033753","article-title":"Shaping Chromatin in the Nucleus: The Bricks and the Architects","volume":"82","author":"Sitbon","year":"2017","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1038\/srep07115","article-title":"Crystal Structure and Stable Property of the Cancer-Associated Heterotypic Nucleosome Containing CENP-A and H3.3","volume":"4","author":"Arimura","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"173","article-title":"Thymic Neoplasm: A Rare Disease with a Complex Clinical Presentation","volume":"5","author":"Rashid","year":"2013","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jtho.2021.10.010","article-title":"The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?","volume":"17","author":"Marx","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_18","unstructured":"WHO Classification of Tumours Editiorial Board (2021). Thoracic Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Psilopatis, I., Pergaris, A., Vrettou, K., Theocharis, S., and Troungos, C. (2022). Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074045"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhu, Z., Zhang, S., Yu, D., Yu, H., Liu, L., Cao, X., Wang, L., Gao, H., and Zhu, M. (2011). ShRNA-Targeted Centromere Protein A Inhibits Hepatocellular Carcinoma Growth. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017794"},{"key":"ref_21","first-page":"3511","article-title":"Overexpression and Mistargeting of Centromere Protein-A in Human Primary Colorectal Cancer","volume":"63","author":"Tomonaga","year":"2003","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R72","DOI":"10.1186\/bcr3181","article-title":"Centromere Protein-A, an Essential Centromere Protein, Is a Prognostic Marker for Relapse in Estrogen Receptor-Positive Breast Cancer","volume":"14","author":"McGovern","year":"2012","journal-title":"Breast Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.lungcan.2012.04.007","article-title":"Expression and Prognostic Significance of Centromere Protein A in Human Lung Adenocarcinoma","volume":"77","author":"Wu","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1007\/s13277-013-0860-6","article-title":"Prognostic Value of Centromere Protein-A Expression in Patients with Epithelial Ovarian Cancer","volume":"34","author":"Qiu","year":"2013","journal-title":"Tumour Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R18","DOI":"10.1186\/bcr2487","article-title":"The Expression Level of HJURP Has an Independent Prognostic Impact and Predicts the Sensitivity to Radiotherapy in Breast Cancer","volume":"12","author":"Hu","year":"2010","journal-title":"Breast Cancer Res."},{"key":"ref_26","first-page":"6697","article-title":"Upregulation of Holliday Junction Recognition Protein Predicts Poor Prognosis and Biochemical Recurrence in Patients with Prostate Cancer","volume":"18","author":"Chen","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Valente, V., Serafim, R.B., de Oliveira, L.C., Adorni, F.S., Torrieri, R., Tirapelli, D.P.D.C., Espreafico, E.M., Oba-Shinjo, S.M., Marie, S.K.N., and Pa\u00e7\u00f3-Larson, M.L. (2013). Modulation of HJURP (Holliday Junction-Recognizing Protein) Levels Is Correlated with Glioblastoma Cells Survival. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062200"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1093\/nar\/gkz634","article-title":"DAXX in Cancer: Phenomena, Processes, Mechanisms and Regulation","volume":"47","author":"Mahmud","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41419-021-03870-x","article-title":"HJURP Promotes Proliferation in Prostate Cancer Cells through Increasing CDKN1A Degradation via the GSK3\u03b2\/JNK Signaling Pathway","volume":"12","author":"Lai","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s13046-018-0866-4","article-title":"HJURP Promotes Hepatocellular Carcinoma Proliferation by Destabilizing P21 via the MAPK\/ERK1\/2 and AKT\/GSK3\u03b2 Signaling Pathways","volume":"37","author":"Chen","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.7150\/ijbs.30904","article-title":"HJURP Promotes Epithelial-to-Mesenchymal Transition via Upregulating SPHK1 in Hepatocellular Carcinoma","volume":"15","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"De Tayrac, M., Saikali, S., Aubry, M., Bellaud, P., Boniface, R., Quillien, V., and Mosser, J. (2013). Prognostic Significance of EDN\/RB, HJURP, P60\/CAF-1 and PDLI4, Four New Markers in High-Grade Gliomas. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073332"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41419-020-2595-9","article-title":"Holliday Junction Recognition Protein Promotes Pancreatic Cancer Growth and Metastasis via Modulation of the MDM2\/P53 Signaling","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kang, D.H., Woo, J., Kim, H., Kim, S.Y., Ji, S., Jaygal, G., Ahn, T.S., Kim, H.J., Kwak, H.J., and Kim, C.-J. (2020). Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217928"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Verrelle, P., Meseure, D., Berger, F., Forest, A., Lecl\u00e8re, R., Nicolas, A., Fortas, E., Sastre-Garau, X., Lae, M., and Boudjemaa, S. (2021). CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients. Cancers, 13.","DOI":"10.3390\/cancers13163928"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"40654","DOI":"10.18632\/oncotarget.17204","article-title":"Motifs in the Amino-Terminus of CENP-A Are Required for Its Accumulation within the Nucleus and at the Centromere","volume":"8","author":"Jing","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.humpath.2011.11.003","article-title":"High Expression of Trimethylated Histone H3 Lysine 4 Is Associated with Poor Prognosis in Hepatocellular Carcinoma","volume":"43","author":"He","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Beyer, S., Zhu, J., Mayr, D., Kuhn, C., Schulze, S., Hofmann, S., Dannecker, C., Jeschke, U., and Kost, B.P. (2017). Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030477"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1158\/0008-5472.CAN-09-2942","article-title":"Hypoxia Induces Trimethylated H3 Lysine 4 by Inhibition of JARID1A Demethylase","volume":"70","author":"Zhou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1007\/s00432-020-03265-z","article-title":"Expression of H3K4me3 and H3K9ac in Breast Cancer","volume":"146","author":"Berger","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1002\/ijc.25250","article-title":"Prognostic Relevance of Global Histone H3 Lysine 4 (H3K4) Methylation in Renal Cell Carcinoma","volume":"127","author":"Ellinger","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E290","DOI":"10.1111\/j.1464-410X.2011.10203.x","article-title":"Global Histone H4K20 Trimethylation Predicts Cancer-Specific Survival in Patients with Muscle-Invasive Bladder Cancer","volume":"108","author":"Schneider","year":"2011","journal-title":"BJU Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e202007195","DOI":"10.1083\/jcb.202007195","article-title":"CENP-A Overexpression Promotes Aneuploidy with Karyotypic Heterogeneity","volume":"220","author":"Shrestha","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mahlke, M.A., and Nechemia-Arbely, Y. (2020). Guarding the Genome: CENP-A-Chromatin in Health and Cancer. Genes, 11.","DOI":"10.3390\/genes11070810"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Arbour, K.C., Naidoo, J., Steele, K.E., Ni, A., Moreira, A.L., Rekhtman, N., Robbins, P.B., Karakunnel, J., Rimner, A., and Huang, J. (2017). Expression of PD-L1 and Other Immunotherapeutic Targets in Thymic Epithelial Tumors. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182665"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An Enhanced Web Server for Large-Scale Expression Profiling and Interactive Analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for Analysis of Tumor-Infiltrating Immune Cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The catalogue of somatic mutations in cancer","volume":"47","author":"John","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:21Z","timestamp":1760140701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":49,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158339"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158339","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}