| Summary: | Abstract Background In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored. Methods LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments. Results The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP. Conclusion Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease.
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