Immune classification and identification of prognostic genes for uveal melanoma based on six immune cell signatures

Sci Rep. 2021 Nov 15;11(1):22244. doi: 10.1038/s41598-021-01627-2.

Abstract

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients' response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Cluster Analysis
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Immune Checkpoint Proteins / genetics
  • Immune Checkpoint Proteins / metabolism
  • Immunomodulation / genetics*
  • Melanoma / etiology*
  • Melanoma / metabolism
  • Melanoma / mortality*
  • Melanoma / therapy
  • Molecular Sequence Annotation
  • Molecular Targeted Therapy
  • Proportional Hazards Models
  • ROC Curve
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transcriptome*
  • Uveal Neoplasms / etiology*
  • Uveal Neoplasms / metabolism
  • Uveal Neoplasms / mortality*
  • Uveal Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Proteins

Supplementary concepts

  • Uveal melanoma