Analysis and experimental validation of disulfidptosis related genes solute carrier family 3 member 2 (SLC3A2) in endometrial cancer

Abstract

Abstract Disulfidptosis, a novel cell death paradigm triggered by disulfide stress, remains underexplored, particularly its implications for endometrial cancer (EC). This study focused on the prognostic significance of disulfidptosis-related genes (DRGs) in EC, highlighting the pivotal role of SLC3A2. To predict EC patient outcomes, we developed a model centered on DRGs, employing LASSO-Cox regression for its construction. The model revealed a strong correlation between DRG risk score, gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), clinical characteristics, the tumor microenvironment (TME), and the response to immunotherapy. Key genes were pinpointed using random forest maps. To establish SLC3A2's oncogenic effects in EC, we conducted comprehensive studies including apoptosis, cell cycle, TRANSWELL, CCK-8, and tumor xenograft assays. SLC3A2 expression was further confirmed via qRT-PCR. The impact of SLC3A2 on EC's malignant behavior was corroborated through both in vitro and in vivo experiments.

Keywords

• Endometrial carcinoma (EC)
• Disulfidptosis-related genes (DRGs)
• Prognostic model
• Tumor microenvironment (TME)
• Carrier family 3 member 2 (SLC3A2)