Identification of a novel disulfideptosis-related gene signature for prognostic implication in lower-grade gliomas

Area of Science:

• Oncology
• Molecular Biology
• Cell Death Research

Background:

• Lower-grade gliomas (GBMLGG) are aggressive brain tumors with limited treatment options.
• Disulfideptosis, a recently identified programmed cell death pathway driven by disulfide metabolism, presents a potential new avenue for cancer therapy.
• Identifying novel therapeutic targets and prognostic markers for GBMLGG is crucial due to treatment constraints.

Purpose of the Study:

• To investigate the prognostic significance of disulfideptosis-related genes in GBMLGG.
• To identify key genes and develop predictive models for GBMLGG patient outcomes.
• To validate the role of identified genes in GBMLGG progression.

Main Methods:

• Analysis of mRNA expression and clinical data from GBMLGG patients in TCGA and GEO databases.
• Differential gene expression analysis to identify prognostic markers.
• Construction of a nomogram model for predicting GBMLGG patient outcomes.
• In vivo and in vitro experiments to validate the function of IQGAP1.

Main Results:

• Significant differential expression of multiple disulfideptosis-related genes was observed between normal and GBMLGG tissues.
• IQ motif-containing GTPase-activating protein 1 (IQGAP1) was identified as a key gene significantly associated with GBMLGG prognosis.
• A nomogram model incorporating disulfideptosis-related genes demonstrated predictive capability for GBMLGG patient survival.
• In vivo and in vitro studies confirmed the cancer-promoting role of IQGAP1 in GBMLGG.

Conclusions:

• A novel gene signature associated with disulfideptosis can effectively predict overall survival (OS) in GBMLGG patients.
• Targeting disulfideptosis represents a promising therapeutic strategy for managing GBMLGG.
• IQGAP1 is a potential therapeutic target and prognostic biomarker for GBMLGG.