Molecular function validation and prognostic value analysis of the cuproptosis-related gene ferredoxin 1 in papillary...

Cuproptosis, a copper-dependent distinct form of cell death, holds a critical role in tumor development. However, further investigation is needed to elucidate the impact of the cuproptosis signaling on thyroid cancer. In this study, comprehensive bioinformatics analyses with six independent cohorts and in vitro experiments were performed to explore the expression, prognostic significance, and molecular function of the cuproptosis key regulator FDX1 in papillary thyroid carcinoma (PTC). LASSO regression analyses were utilized to screen the optimal combination of cuproptosis-related genes for constructing a Cox proportional-hazards model, and the cuproptosis-related risk score (CRRS) was calculated to stratify PTC patients in prognosis. The algorithm of ESTIMATE and ssGSEA were used to investigate the tumor immune microenvironment. Our results showed FDX1 was significantly downregulated in PTC, and its lower expression was closely associated with tumor recurrence. Based on six selected cuproptosis-related genes a predictive prognosis model was established and CRRS displayed a good prediction accuracy. Overexpression of FDX1 could promote cell death and inhibit the viability of tumor cells. Additionally, CYCS played a hub role in the cuproptosis regulatory network and could be upregulated with the overexpression of FDX1. Our study suggests that CRRS can serve as a good prognosis indicator and may provide new insights into cuproptosis-targeted therapies in PTC.