Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms

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...

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Main Authors: Georgia Levidou, Konstantinos Palamaris, Alexandros G. Sykaras, Georgios Andreadakis, Christos Masaoutis, Irene Theochari, Penelope Korkolopoulou, Dimitra Rontogianni, Stamatios Theocharis
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/15/8339
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author Georgia Levidou
Konstantinos Palamaris
Alexandros G. Sykaras
Georgios Andreadakis
Christos Masaoutis
Irene Theochari
Penelope Korkolopoulou
Dimitra Rontogianni
Stamatios Theocharis
author_facet Georgia Levidou
Konstantinos Palamaris
Alexandros G. Sykaras
Georgios Andreadakis
Christos Masaoutis
Irene Theochari
Penelope Korkolopoulou
Dimitra Rontogianni
Stamatios Theocharis
author_sort Georgia Levidou
collection DOAJ
description 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 (<i>p</i> = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (<i>p</i> = 0.007 and <i>p</i> = 0.002) and higher cytoplasmic HJURP H-score (<i>p</i> < 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka–Koga stage (<i>p</i> = 0.048 and <i>p</i> < 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 (<i>p</i> = 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.
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spelling doaj.art-bd6356ee7ab84267b42d9a16ddef88dd2023-11-30T22:25:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315833910.3390/ijms23158339Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial NeoplasmsGeorgia Levidou0Konstantinos Palamaris1Alexandros G. Sykaras2Georgios Andreadakis3Christos Masaoutis4Irene Theochari5Penelope Korkolopoulou6Dimitra Rontogianni7Stamatios Theocharis8First Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Pathology, National and Kapodistrian University of Athens, 11527 Athens, GreeceBackground: 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 (<i>p</i> = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (<i>p</i> = 0.007 and <i>p</i> = 0.002) and higher cytoplasmic HJURP H-score (<i>p</i> < 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka–Koga stage (<i>p</i> = 0.048 and <i>p</i> < 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 (<i>p</i> = 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.https://www.mdpi.com/1422-0067/23/15/8339thymic epithelial neoplasmsthymomashistonesCENP-AHJURPDAXX
spellingShingle Georgia Levidou
Konstantinos Palamaris
Alexandros G. Sykaras
Georgios Andreadakis
Christos Masaoutis
Irene Theochari
Penelope Korkolopoulou
Dimitra Rontogianni
Stamatios Theocharis
Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
International Journal of Molecular Sciences
thymic epithelial neoplasms
thymomas
histones
CENP-A
HJURP
DAXX
title Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
title_full Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
title_fullStr Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
title_full_unstemmed Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
title_short Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms
title_sort unraveling the role of histone variant cenp a and chaperone hjurp expression in thymic epithelial neoplasms
topic thymic epithelial neoplasms
thymomas
histones
CENP-A
HJURP
DAXX
url https://www.mdpi.com/1422-0067/23/15/8339
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