Identification of an anoikis-related gene signature and characterization of immune infiltration in skin cutaneous melanoma.

ABSTRACT

Anoikis is considered strongly associated with a biological procession of tumors. Herein, we utilized anoikis-related genes (ARGs) to predict the prognosis and immunotherapeutic efficacy for skin cutaneous melanoma (SKCM). RNA-seq data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. After dividing patients into novel subtypes based on the expression of prognostic ARGs, K-M survival was conducted to compare the survival status. Subsequently, differentially expressed ARGs were identified and the predictive model was established. The predictive effects were validated using the areas under the curve about the receiver operating characteristic. Moreover, tumor mutation burden, the enriched functional pathway, immune cells and functions, and the immunotherapeutic response were also analyzed and compared. The distribution of model genes at cell level was visualized by the single-cell seq with tumor immune single-cell hub database. Patients of The Cancer Genome Atlas-SKCM cohort were divided into 2 clusters, the cluster 1 performed a better prognosis. Cluster 2 was more enriched in metabolism-related pathways whereas cluster 1 was more associated with immune pathways. A predictive risk model was established with 6 ARGs, showing the areas under the curves of 1-year, 3-year, and 5-year ROC were 0.715, 0,720, and 0.731, respectively. Moreover, risk score was negatively associated with tumor mutation burden and immune-related pathways enrichment. In addition, patients with high-risk scores performed immunosuppressive status but the decreasing scores enhanced immune cell infiltration, immune function activation, and immunotherapeutic response. In this study, we established a novel signature in predicting prognosis and immunotherapy. It can be considered reliable to formulate the complex treatment for SKCM patients.