Identification and validation of an immune-relevant risk signature predicting survival outcome and immune infiltration in uveal melanoma.

PURPOSE

The current study aimed to reveal a novel immune-related signature to evaluate immune infiltration status and the survival outcome for patients with uveal melanoma (UM).

METHODS

Based on 80 UM samples from the Cancer Genome Atlas, the transcriptome gene expression and clinical characteristics were analyzed to identify immune-related genes that contributed most to prognosis based on LASSO Cox regression. By combining the gene expression level with the corresponding regression coefficient, a risk score was calculated and all patients were divided into high- and low-risk groups. Survival, tumor-infiltrating immune cell abundance, dysregulated signaling pathways, immunophenoscore and tumor mutation burden were compared between two groups. Validation of the risk signature was performed in GSE22138 and GSE44295 cohort. For evaluating the immunotherapy efficacy, 348 advanced urothelial cancer patients treated with immune checkpoint inhibitor (ICI) were used for external validation.

RESULTS

Nine immune-related prognostic genes were identified under the LASSO Cox regression in the TCGA cohort; they are ACKR2, AREG, CCL5, CLEC11A, IGKV1-33, IL36B, NROB1, TRAV8-4 and TRBV28. Better prognosis, elevated immune cell infiltration, decreased immune-suppressive cell infiltration, immune response-related pathways and higher immunophenoscore were found in low-risk patients, with better ICI treatment response rate.

CONCLUSION

The identified immune risk signature was demonstrated to be associated with the favorable immune infiltration, prognosis and immunotherapeutic efficacy, which may provide clues for survival evaluation and immune treatment.