Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis

Aging (Albany NY). 2020 Jan 18;12(2):1446-1464. doi: 10.18632/aging.102693. Epub 2020 Jan 18.

Abstract

Uveal melanoma is an aggressive intraocular malignancy that often exhibits low immunogenicity. Metastatic uveal melanoma samples frequently exhibit monosomy 3 or BAP1 deficiency. In this study, we used bioinformatic methods to investigate the immune infiltration of uveal melanoma samples in public datasets. We first performed Gene Set Enrichment/Variation Analyses to detect immunological pathways that are altered in tumors with monosomy 3 or BAP1 deficiency. We then conducted an unsupervised clustering analysis to identify distinct immunologic molecular subtypes of uveal melanoma. We used CIBERSORT and ESTIMATE with RNA-seq data from The Cancer Genome Atlas and the GSE22138 microarray dataset to determine the sample-level immune subpopulations and immune scores of uveal melanoma samples. The Kaplan-Meier method and log-rank test were used to assess the prognostic value of particular immune cells and genes in uveal melanoma samples. Through these approaches, we discovered uveal melanoma-specific immunologic features, which may provide new insights into the tumor microenvironment and enhance the development of immunotherapies in the future.

Keywords: TCGA; bioinformatics; immune cell fractions; immune subtype; uveal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunity*
  • Immunomodulation / genetics
  • Male
  • Melanoma / diagnosis
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / mortality*
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism
  • Uveal Melanoma
  • Uveal Neoplasms / diagnosis
  • Uveal Neoplasms / immunology*
  • Uveal Neoplasms / metabolism
  • Uveal Neoplasms / mortality*
  • Young Adult

Substances

  • BAP1 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase