Deciphering cutaneous melanoma prognosis through LDL metabolism: Single‐cell transcriptomics analysis via 101 machine learning algorithms

Abstract Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic and molecular contributors to cutaneous melanoma development, there remains a critical knowledge gap concerning the role of lipids, notably low‐density lipoprotein (LDL), in this lethal skin cancer. This article endeavours to bridge this knowledge gap by delving into the intricate interplay between LDL metabolism and cutaneous melanoma, shedding light on how lipids influence tumour progression, immune responses and potential therapeutic avenues. Genes associated with LDL metabolism were extracted from the GSEA database. We acquired and analysed single‐cell sequencing data (GSE215120) and bulk‐RNA sequencing data, including the TCGA data set, GSE19234, GSE22153 and GSE65904. Our analysis unveiled the heterogeneity of LDL across various cell types at the single‐cell sequencing level. Additionally, we constructed an LDL‐related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes and highly correlated genes. The LRS serves as a valuable tool for assessing the prognosis, immunity and mutation status of patients with cutaneous melanoma. Furthermore, we conducted experiments on A375 and WM‐115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.