Association Between FSIP2 Mutation and an Improved Prognosis in Patients With Skin Cutaneous Melanoma Treated With Immune Checkpoint Inhibitors

Abstract

Background Immune checkpoint inhibitors (ICIs) have been remarkably successful in skin cutaneous melanoma (SKCM), however the response to treatment varies greatly among different patients. Considering that the efficacy of ICI treatment is affected by many factors, we selected the Fibrosheath interacting protein 2 (FSIP2) gene and systematically analyzed its potential as a predictor of ICI treatment prognosis. Methods Patient data were collected from an ICI treatment cohort (n = 120) and The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 467). The data was divided into an FSIP2-mutant (MT) group and FSIP2-wild-type (WT) group according to the FSIP2 mutation status. In this study we analyzed the patients’ overall survival rate, tumor mutational burden (TMB), neoantigen load (NAL), copy number variation (CNV), cell infiltration data and immune-related genes. We used gene set enrichment analysis (GSEA) to delineate biological pathways and processes associated with the prognosis of immunotherapy. Results The prognosis of SKCM patients with FSIP2-MT receiving ICIs was significantly better than that of those with FSIP2-WT. The patients in the FSIP2-MT group had higher tumor immunogenicity and lower regulatory T cell (Treg) infiltration. Results of GSEA showed that pathways related to tumor progression (MAPK and FGFR), immunomodulation, and IL-2 synthesis inhibition were significantly downregulated in the FSIP2-MT group. Conclusion Our research suggests that the FSIP2 gene has the potential to predict the prognosis of ICI treatment. The higher tumor immunogenicity and lower Treg levels may be closely related to the fact that patients with FSIP2-MT can benefit more from ICI treatment.