Identification of Biomarkers with Therapeutic And prognostic Value in Skin Cutaneous Melanoma

Abstract Background The morbidity and mortality of skin cutaneous melanoma (SKCM), the most deadly type of skin cancer, are on the rise worldwide. Through in-depth study of the tumor microenvironment (TME) of SKCM, this study further identified biomarkers with therapeutic and prognostic value. Methods The gene expression profiles and clinical data of SKCM patients were downloaded from The Cancer Genome Atlas database. Then we calculated the immune score and stromal score of patients with skin melanoma by using the estimate algorithm, and divided all patients into the high/low immune/stromal score groups and discussed the correlation between them and clinical characteristics.Then, limma R package was used to screen out the differential genes in the high/low immune/ stromal score groups, and the heat map of the differential genes was drawn. At the same time, the functional enrichment analysis of the differential genes was carried out. The protein‒protein interaction (PPI) network of different genes was constructed by using STRING and Cytoscape, and the key genes related to the prognosis of cutaneous melanoma were further selected. Finally, kinase target, co expression genes and immune infiltrating cells of key genes were discussed. Results Patients in the low-immune/stromal score group had poorer survival outcome. The immune and stromal scores are associated with specific clinicopathologic variables (age, tumor grade, tumor stage) in SKCM. In total, 914 DEGs (909 upregulated and 5 downregulated genes) were screened from the gene expression profiles of patients with high immune and stromal scores. Functional enrichment analysis demonstrated a correlation between DEGs and the tumor microenvironment, tumor immune response and RCC tumorigenesis.Kaplan-Meier survival curves showed that 15 out of the 914 identified tumor microenvironment related genes are involved in the prognosis of SKCM. Finally CXCR8 and CCR5 were selected as the hub genes. A positive correlation was obtained between the expression of CXCR8/CCR5 and the abundance of six immune cells. Conclusions We studied the tumor microenvironment of SKCM, and finally screened out the biomarkers with therapeutic and prognostic effects.