Research Paper Volume 12, Issue 2 pp 1446—1464
Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis
- 1 Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
- 2 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
- 3 Department of Pathology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
Received: October 20, 2019 Accepted: December 25, 2019 Published: January 18, 2020
https://doi.org/10.18632/aging.102693How to Cite
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.
Abbreviations
AJCC: American Joint Committee on Cancer stage; ANOVA: analysis of variance; CIBERSORT: Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts; CM: cutaneous melanoma; D3: Disomy3; ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data; FPKM: Fragments Per Kilobase of transcript per Million fragments mapped; GSEA/GSVA: Gene Set Enrichment/Variation Analysis; HR: hazard ratio; IR: Ionizing radiation; M3: Monosomy3; PFI: Progression-free interval; SCNA: somatic copy number alteration; TCGA: The Cancer Genome Atlas; UM: Uveal melanoma.