Research Paper Volume 16, Issue 7 pp 6054—6067

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

Fuqiang Zhang1, , Meihong Lv2, , Yi He3, ,

  • 1 Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
  • 2 Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
  • 3 Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China

Received: July 11, 2023       Accepted: February 20, 2024       Published: March 27, 2024      

https://doi.org/10.18632/aging.205688
How to Cite

Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lower-grade gliomas (GBMLGG) are common, fatal, and difficult-to-treat cancers. The current treatment choices have impressive efficacy constraints. As a result, the development of effective treatments and the identification of new therapeutic targets are urgent requirements. Disulfide metabolism is the cause of the non-apoptotic programmed cell death known as disulfideptosis, which was only recently discovered. The mRNA expression data and related clinical information of GBMLGG patients downloaded from public databases were used in this study to investigate the prognostic significance of genes involved in disulfideptosis. In the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohort, our findings showed that many disulfidptosis-related genes were expressed differently in normal and GBMLGG tissues. It was discovered that IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a key gene that influences the outcome of GBMLGG. Besides, a nomogram model was built to foresee the visualization of GBMLGG patients. In addition, in vivo and in vitro validation of IQGAP1’s cancer-promoting function was done. In conclusion, we discovered a gene signature associated with disulfideptosis that can effectively predict OS in GBMLGG patients. As a result, treating disulfideptosis may be a viable alternative for GBMLGG patients.

Abbreviations

GBMLGG: Lower-grade gliomas; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; IQGAP1: IQ motif-containing GTPase-activating protein 1; IDH: isocitrate dehydrogenase; GBMHGG: High-grade gliomas; PFS: progression-free survival; PCD: programmed cell death; GAP: GTPase-activating protein; UALCAN: The University of Alabama Cancer Database; CPTAC: The Clinical proteomic tumor analysis consortium; ATCC: American Type Culture Collection; PI: propidium iodide; TME: tumor microenvironment; TIICs: tumor infiltrating immune cells; RCD: Regulated cell death; GLUT: Glucose transporter; IHC: Immunohistochemistry.