Integrating bioinformatic analyses and experimental validation of disulfidptosis-related genes and TMX4 in melanoma progression

作者：Yi Yi, Rui Tao, Zeqi Shi, Lan Chen, Zhanyong Zhu, Min Wu · 发表于：Cancer Cell International · 年份：2026 · DOI：10.1186/s12935-026-04182-w · 被引用次数：1 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Hypoxia, and Metabolism、Endoplasmic Reticulum Stress and Disease

BACKGROUND: Melanoma is a highly metastatic and lethal malignancy originating from melanocytes. Disulfidptosis is a recently discovered type of programmed cell death with promising potential in cancer therapy. This study aims to establish a prognostic risk model based on disulfidptosis-related gene signatures and investigate their roles in melanoma progression. MATERIALS AND METHODS: Transcriptomic data from the TCGA-SKCM and GEO databases were analyzed to identify disulfidptosis-related gene expression profiles in melanoma. Consensus clustering categorized samples into two molecular subtypes, followed by comprehensive analyses of genomic and immune infiltration characteristics. A prognostic risk model was developed using Lasso regression based on DEGs. The expression and function of TMX4 were further validated using IHC and in vitro experiments, including siRNA-mediated knockdown in A375 and A875 melanoma cell lines. Cell proliferation, migration, and indicators of redox homeostasis (GSH, MDA, and ROS) were evaluated, and SLC7A11 expression was measured to explore underlying mechanisms. RESULTS: Melanoma samples were divided into two subtypes with distinct tumor microenvironments. The eight-gene prognostic model accurately predicted patient outcomes in both training and validation cohorts. TMX4 was highly expressed in melanoma tissues, and its knockdown significantly inhibited the proliferation and migration of melanoma cells. Silencing of TMX4 enhanced oxidative stress by r...