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Updated: Jul 10, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Protein Disulfide Isomerase A2 Is Correlated with Immune Infiltrates and Is a Novel Prognostic Biomarker in Glioma
Zhi-Gang Ma1,2, Ying-Xue Liu3, Ning Zou4
1Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Objective:
Protein disulfide isomerase A2 (PDIA2), a member of the protein disulfide isomerase family, plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds, together with enzymes such as thiol isomerase, oxidase, and reductase. This study investigated the clinical significance and potential functions of PDIA2 in glioma.
Methods:
The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases. We analyzed the clinical characteristics of glioma patients and the prognostic and diagnostic value of PDIA2 expression. Kaplan-Meier and Cox regression analyses were used to examine the effect of PDIA2 expression on overall survival, progression-free interval, and disease-specific survival. Furthermore, we performed Gene Set Enrichment Analysis and immune infiltration analysis to investigate the functions of PDIA2. PDIA2 mRNA and protein expression was evaluated in cell lines and glioma tissues.
Results:
PDIA2 was expressed at low levels in glioma patients. Kaplan-Meier survival analysis showed that glioma patients with low PDIA2 levels had a worse prognosis than those with high PDIA2 levels. Receiver operating characteristic curve analysis indicated the diagnostic and prognostic ability of PDIA2 (area under the curve = 0.918). Pathways associated with PD1, PI3K/AKT, cancer immunotherapy via PD1 blockade, Fceri-mediated NF-kB activation, FOXM1, and DNA repair were enriched in glioma patients with low levels of PDIA2. PDIA2 expression levels were negatively correlated with immune cell infiltrate levels.
Conclusion:
PDIA2 levels are significantly downregulated in glioma. PDIA2 expression may be a potential biomarker for the diagnosis and prognosis of glioma patients.
