Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma
One of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the mos...
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doaj-63c879cb9bc243caa399147ec3307ae42020-11-24T21:26:59ZengMDPI AGCancers2072-66942019-08-01118110210.3390/cancers11081102cancers11081102Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal MelanomaZahra Souri0Annemijn P. A. Wierenga1Christiaan van Weeghel2Pieter A. van der Velden3Wilma G. M. Kroes4Gregorius P. M. Luyten5Sjoerd H. van der Burg6Aart G. Jochemsen7Martine J. Jager8Department of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Clinical Oncology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Ophthalmology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsOne of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the most important regulators of inflammation, the NFkB pathway, might play a role. We analyzed 64 UM samples for expression of HLA Class I, its regulators, and of members of the NFkB transcription family, using an Illumina HT12V4 array. HLA Class I expression and infiltrating immune cells were also determined by immunohistochemical staining. Information was obtained regarding chromosome status by Affymetrix Nsp array. Our analysis shows that expression of NFkB1, NFkB2 and RELB positively correlates with the level of HLA Class I expression and the number of infiltrating T cells and macrophages, while SPP1 and PPARγ are negatively correlated. Increased levels of NFkB1 and NFkB2 and decreased levels of SPP1 and PPARγ are seen in Monosomy 3/BAP1-negative tumors. This is also the case in non-inflammatory UM, indicating that our observation not only involves infiltrating leukocytes but the tumor cells themselves. We report that the NFkB pathway is associated with inflammation and HLA Class I expression in UM, and is upregulated when BAP1 expression is lost.https://www.mdpi.com/2072-6694/11/8/1102uveal melanomainflammationHLA Class INFkB pathwayBAP1oncology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zahra Souri Annemijn P. A. Wierenga Christiaan van Weeghel Pieter A. van der Velden Wilma G. M. Kroes Gregorius P. M. Luyten Sjoerd H. van der Burg Aart G. Jochemsen Martine J. Jager |
spellingShingle |
Zahra Souri Annemijn P. A. Wierenga Christiaan van Weeghel Pieter A. van der Velden Wilma G. M. Kroes Gregorius P. M. Luyten Sjoerd H. van der Burg Aart G. Jochemsen Martine J. Jager Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma Cancers uveal melanoma inflammation HLA Class I NFkB pathway BAP1 oncology |
author_facet |
Zahra Souri Annemijn P. A. Wierenga Christiaan van Weeghel Pieter A. van der Velden Wilma G. M. Kroes Gregorius P. M. Luyten Sjoerd H. van der Burg Aart G. Jochemsen Martine J. Jager |
author_sort |
Zahra Souri |
title |
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma |
title_short |
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma |
title_full |
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma |
title_fullStr |
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma |
title_full_unstemmed |
Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma |
title_sort |
loss of bap1 is associated with upregulation of the nfkb pathway and increased hla class i expression in uveal melanoma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-08-01 |
description |
One of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the most important regulators of inflammation, the NFkB pathway, might play a role. We analyzed 64 UM samples for expression of HLA Class I, its regulators, and of members of the NFkB transcription family, using an Illumina HT12V4 array. HLA Class I expression and infiltrating immune cells were also determined by immunohistochemical staining. Information was obtained regarding chromosome status by Affymetrix Nsp array. Our analysis shows that expression of NFkB1, NFkB2 and RELB positively correlates with the level of HLA Class I expression and the number of infiltrating T cells and macrophages, while SPP1 and PPARγ are negatively correlated. Increased levels of NFkB1 and NFkB2 and decreased levels of SPP1 and PPARγ are seen in Monosomy 3/BAP1-negative tumors. This is also the case in non-inflammatory UM, indicating that our observation not only involves infiltrating leukocytes but the tumor cells themselves. We report that the NFkB pathway is associated with inflammation and HLA Class I expression in UM, and is upregulated when BAP1 expression is lost. |
topic |
uveal melanoma inflammation HLA Class I NFkB pathway BAP1 oncology |
url |
https://www.mdpi.com/2072-6694/11/8/1102 |
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