Cutaneous melanoma (CM, hereafter referred to as melanoma) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in melanoma has not been fully elucidated. In this study, we examined the relationship between pyroptosis and the prognosis of melanoma through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with melanoma prognosis. A higher pyroptosis score was associated with a more favorable overall survival. We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively evaluate the prognosis of melanoma. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+ T cells, CD8+ T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of melanoma to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified solute carrier family 31 member 2 (SLC31A2) and collagen type 4 alpha 5 chain (COL4A5) as being associated with resistance to most of these drugs. In conclusion, this PGS is an effective and novelty prognostic indicator in melanoma, and also has an association with the melanoma immune microenvironment and melanoma treatment decision-making.

Skin cutaneous melanoma (SKCM) is a highly malignant tumor that typically undergoes early metastasis. Pyroptosis, as a special programmed cell death process that releases inflammatory factors and has been widely studied in tumors, but its role in SKCM has not been fully elucidated. In this present study, we examined the relationship between pyroptosis and the prognosis of SKCM through bioinformatic analysis of RNA-sequencing data. Our results demonstrated that pyroptosis is a protective factor associated with SKCM prognosis. A higher pyroptosis score was associated with a more favorable overall survival (OS). We used weighted gene co-expression networks analysis (WGCNA) to establish an effective prognosis prediction model based on 12 pyroptosis-related genes. We then validated it in two independent cohorts. Furthermore, a nomogram combining clinicopathological characteristics and a pyroptosis-related gene signature (PGS) score was designed to effectively predict the prognosis of SKCM. Additionally, we analyzed the potential roles of pyroptosis in the tumor immune microenvironment and drug response. Interestingly, we found that the elevated infiltration of multiple immune cells, such as CD4+T cells, CD8+T cells, dendritic cells, and M1 macrophages, may be associated with the occurrence of pyroptosis. Pyroptosis was also related to a better response of these lesions to interferon-α, paclitaxel, cisplatin and imatinib. Through Spearman correlation analysis of the 12 pyroptosis-related genes and 135 chemotherapeutic agents in the Genomics of Drug Sensitivity in Cancer database, we identified SLC31A2 and COL4A5 as being associated with resistance to most of these drugs. In conclusion, the PGS is an effective prognostic indicator in SKCM, and also has an association with the SKCM immune microenvironment and drug response.

Cutaneous melanoma is widely known to be the most lethal of skin tumors. Cuproptosis is a newly discovered cell death form which is related to the process of oxidative phosphorylation. However, the exact involvement of cuproptosis in melanoma is unknown. Our research explored the potential relationship between cuproptosis-related genes with prognosis, immune microenvironments, and treatments of melanoma. The cuproptosis regulators differ substantially in melanoma and normal tissues. Additionally, cuproptosis regulators are associated with melanoma. The newly established cuproptosis-related gene signature (CGS) could effectively predict overall survival (OS) of melanoma, and a novel nomogram combining clinical characteristics with CGS was constructed. Further, CD8 + T cells, Tfh cells, B cells, and myeloid-derived suppressor cells were correlated with the CGS. Among the CGS, Peptidylprolyl isomerase C (PPIC) was most associated with melanoma’s poor prognosis and drug resistance. PPIC can promote melanoma progression by enhancingmelanoma cell invasiveness and decreasing CD8 + T cell activation. The current study revealed the correlation between CGS with melanoma prognosis, immune microenvironment, and drug resistance. Moreover, our study provided new data that supports PPIC as a potential and efficient biomarker for OS prognosis in the treatment of melanoma.