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Article

Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma

by 1,2,3,* and 3,4
1
Department of Epidemiology, University of California Irvine, Irvine, CA 92697, USA
2
Department of Medicine, University of California Irvine, Irvine, CA 92697, USA
3
Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA 92697, USA
4
Department of Population Health and Disease Prevention, University of California Irvine, Irvine, CA 92697, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(2), 411; https://doi.org/10.3390/jcm9020411
Received: 28 December 2019 / Revised: 29 January 2020 / Accepted: 30 January 2020 / Published: 3 February 2020
(This article belongs to the Section Dermatology)
Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes. View Full-Text
Keywords: uveal melanoma; cutaneous melanoma; BAP1; overall survival; age difference uveal melanoma; cutaneous melanoma; BAP1; overall survival; age difference
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MDPI and ACS Style

Liu-Smith, F.; Lu, Y. Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma. J. Clin. Med. 2020, 9, 411. https://doi.org/10.3390/jcm9020411

AMA Style

Liu-Smith F, Lu Y. Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma. Journal of Clinical Medicine. 2020; 9(2):411. https://doi.org/10.3390/jcm9020411

Chicago/Turabian Style

Liu-Smith, Feng, and Yunxia Lu. 2020. "Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma" Journal of Clinical Medicine 9, no. 2: 411. https://doi.org/10.3390/jcm9020411

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