Identification of Glutathione Synthetase as a Therapeutic Target for Cervical Cancer via Combining Bioinformatics and Experimental Validation

ABSTRACT

Cervical cancer remains a leading cause of cancer‐related mortality among women worldwide, posing a severe threat to female health. Previous research indicates that cuproptosis is a copper‐dependent form of regulated cell death, holding potential as a therapeutic avenue. This study aimed to identify and validate Cuproptosis‐Related Genes (CRGs) as biomarkers and therapeutic targets in cervical cancer. Transcriptomic data from TCGA and GTEx databases were analysed alongside curated literature data, leading to the identification of 67 pivotal CRGs. Diagnostic and prognostic models were constructed using machine learning algorithms and LASSO‐Cox regression, respectively. Glutathione synthetase (GSS) was selected for subsequent functional validation in cellular assays. Drug sensitivity analysis, mechanistic investigations and in vivo experiments were conducted to evaluate therapeutic potential. Statistical analyses were performed using R and GraphPad Prism. Our analysis identified GSS as a core gene. Functional experiments showed that GSS promotes cervical cancer cell proliferation and invasion under cuproptosis‐inducing conditions. Drug sensitivity analysis linked GSS to vorinostat, which inhibits tumour growth by suppressing the PI3K/Akt pathway and downregulating GSS. These findings were confirmed in both in vitro and in vivo studies. This study identifies GSS as a key cuproptosis regulator and a promising therapeutic target in cervical cancer, suggesting a novel precision medicine strategy.