Identification of CAPG as a potential prognostic biomarker associated with immune cell infiltration and ferroptosis in uterine corpus endometrial carcinoma
Introduction: Capping actin protein, gelsolin-like (CAPG), has been identified as a potential therapeutic target in various cancers. However, its immunotherapeutic implications and prognostic significance in uterine corpus endometrial carcinoma (UCEC) remain poorly understood.
Methods: This study explored the role of CAPG in UCEC through a comprehensive analysis using multiple public databases and online tools. We investigated its characterization, methylation effects, prognostic value, targeted miRNAs, and associations with immune cell infiltration and ferroptosis. Functional studies included EdU and Transwell migration assays to evaluate the physiological role of CAPG, immunofluorescence to determine its localization and expression alongside GPX4, and FerroOrange probes to measure intracellular Fe²⁺ levels in Ishikawa cells. Additionally, the OncoPredict package was employed to identify potential chemotherapeutic agents for UCEC treatment.
Results: CAPG expression was significantly elevated in tumor tissues. Patients in the high-risk group, defined by CAPG expression, exhibited a markedly lower overall survival rate compared to the low-risk group. Enrichment analysis revealed that CAPG is involved in immune-related pathways and plays a crucial role in the tumor microenvironment. Its expression was influenced by abnormal DNA methylation and miRNA regulation, and it was strongly correlated with immune cell infiltration, immune-related gene markers, and ferroptosis. Ferroptosis analysis identified ALOX5 and VLDLR as key GSK864 CAPG-related markers, with glutathione metabolism levels elevated in tumor samples. Decitabine was found to act as a ferroptosis inducer. Knockdown of CAPG via siRNA suppressed cell proliferation and invasion, upregulated immune-related genes (IL8, TNF, TLR4), and increased intracellular Fe²⁺ levels. Immunofluorescence showed that CAPG co-localized with GPX4 in the nucleus, co-regulating ferroptosis and metabolism in Ishikawa cells. Furthermore, four chemotherapeutic agents demonstrated higher sensitivity in low-risk UCEC cohorts.
Conclusions: CAPG plays a pivotal role in regulating immune response and ferroptosis in UCEC, highlighting its potential as a biomarker and therapeutic target. These findings provide new insights into the development of combined immunotherapy strategies for UCEC.