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Protein Disulfide Isomerase A2 Is Correlated with Immune Infiltrates and Is a Novel Prognostic Biomarker in Glioma Patients

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Abstract

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.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Zhi-gang Ma, Zhe Huang, Ming Wang, Jie Zhou & Li-gang Chen

  2. Sichuan Clinical Medical Research Center for Neurosurgery, Luzhou, 646000, China

    Zhi-gang Ma, Zhe Huang, Ming Wang, Jie Zhou & Li-gang Chen

  3. School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, China

    Ying-xue Liu

  4. Department of Laboratory, People’s Hospital of Deyang City, Deyang, 618000, China

    Ning Zou

  5. Laboratory of Mitochondria and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, China

    Tao Li

  6. Neurological Diseases and Brain Function Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Jie Zhou & Li-gang Chen

  7. Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China

    Jie Zhou & Li-gang Chen

Authors
  1. Zhi-gang Ma
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  2. Ying-xue Liu
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  3. Ning Zou
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  4. Zhe Huang
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  5. Ming Wang
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  6. Tao Li
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  7. Jie Zhou
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  8. Li-gang Chen
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Corresponding author

Correspondence to Li-gang Chen.

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The authors declare no conflicts of interest in the study.

Additional information

This study was supported by grants from the Natural Science Foundation of Southwest Medical University (No. 2016XNYD217, No. 2018-ZRQN-032 and No. 2016LZXNYD-G03), the National Natural Science Foundation of China (No. 82072780) and Sichuan Science and Technology Program (No. 2022YFS0630).

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Ma, Zg., Liu, Yx., Zou, N. et al. Protein Disulfide Isomerase A2 Is Correlated with Immune Infiltrates and Is a Novel Prognostic Biomarker in Glioma Patients. CURR MED SCI 43, 1107–1115 (2023). https://doi.org/10.1007/s11596-023-2790-x

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  • DOI: https://doi.org/10.1007/s11596-023-2790-x

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