Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma

Cancers
Zahra SouriMartine J Jager

Abstract

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 ...Continue Reading

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Citations

Jul 25, 2019·Cancers·Niels J BrouwerMartine J Jager
Jul 22, 2019·Cancers·Niels J BrouwerMartine J Jager
Aug 10, 2019·Cancers·Christiaan van WeeghelMartine J Jager
Dec 15, 2019·Cancers·Ulrich Pfeffer
Jul 1, 2020·Acta Pharmacologica Sinica·Chen-Xi ZhaoHong Zhu
Dec 23, 2020·International Journal of Molecular Sciences·Andrea SoltysovaBozena Smolkova
Dec 16, 2020·Cancers·Asad Javed, Mohammed Milhem
Mar 3, 2021·Expert Opinion on Investigational Drugs·Christos MasaoutisStamatios Theocharis

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Methods Mentioned

BETA
xenograft
xenografts

Software Mentioned

SPSS
GraphPad Prism
GraphPad

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