Abstract
Ferroptosis is a non-apoptotic regulated cell death process, and much research has indicated that ferroptosis can induce the non-apoptotic death of tumor cells. Ferroptosis-related genes are expected to become a biological target for cancer treatment. However, the regulation of ferroptosis-related genes in skin cutaneous melanoma (SKCM) has not been well studied. In the present study, we conducted a systematic analysis of SKCM based on RNA sequencing data and clinical data obtained from The Cancer Genome Atlas (TCGA) database and the FerrD database. SKCM patients from the GSE78220 and MSKCC cohorts were used for external validation. Applying consensus clustering on RNA sequencing data from TCGA the generated ferroptosis subclasses of SKCM, which were analyzed based on the set of differentially expressed ferroptosis-related genes. Then, a least absolute shrinkage and selection operator (LASSO)-Cox regression was used to construct an eight gene survival-related linear signature. The median cut-off risk score was used to divide patients into high- and low-risk groups. The time-dependent receiver operating characteristic curve was used to examine the predictive power of the model. The areas under the curve of the signature at 1, 3, and 5 years were 0.673, 0.716, and 0.746, respectively. Kaplan-Meier survival analysis showed that the prognosis of high-risk patients was worse than that of low-risk patients. Univariate and multivariate Cox regression analyses showed that the risk signature was a robust independent prognostic indicator. By incorporating risk scores with tumor staging, a nomogram was constructed to predict prognostic outcomes for SKCM patients. In addition, the immunological analysis showed different immune cell infiltration patterns. Programmed-death-1 (PD-1) immunotherapy showed more significant benefits in the low-risk group than in the high-risk group. In summary, a model based on ferroptosis-related genes can predict the prognosis of SKCM and could have a potential role in guiding targeted therapy of SKCM.
Highlights
Human skin cutaneous melanoma (SKCM) is a highly malignant tumor derived from melanocytes, that is prone to occur in adults
Surgical resection is associated with a satisfactory prognosis for melanoma in the early stages, while treatment of metastatic melanoma mainly relies on immunotherapy (Leonardi et al, 2020)
The results showed that the expression of GCH1 significantly correlated with macrophage M1 cells, CD8+ T cells, and activated CD4+ memory T cells (Figure 5B)
Summary
Human skin cutaneous melanoma (SKCM) is a highly malignant tumor derived from melanocytes, that is prone to occur in adults. Early-stage, localized melanoma can be curable if appropriate and sufficient treatment is administered (Coit et al, 2013) ; the tumor tends to metastasize and spread to other parts of the body (Aris and Barrio, 2015), once metastasized, the 5-years survival rate decreases to only 15% (Coit et al, 2013). Surgical resection is associated with a satisfactory prognosis for melanoma in the early stages, while treatment of metastatic melanoma mainly relies on immunotherapy (Leonardi et al, 2020). Many studies have explored the relationship between cancer cells, the tumor microenvironment (TME), and the immune system. Identifying robust predictive biomarkers for both clinical prognosis and treatment response is essential
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