PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas.
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ enzymology
Cell Line, Tumor
Cell Proliferation
Coculture Techniques
Databases, Genetic
Glioma
/ enzymology
Humans
Immunotherapy
Prognosis
Protein Disulfide-Isomerases
/ genetics
Tumor Microenvironment
Tumor-Associated Macrophages
/ immunology
Up-Regulation
PDIA5
gliomas
immune infiltration
immunotherapy
scRNA-seq
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
13
11
2020
accepted:
04
01
2021
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
16
9
2021
Statut:
epublish
Résumé
Gliomas are the most common and lethal primary malignant tumor of the brain. Routine treatment including surgical resection, chemotherapy, and radiotherapy produced limited therapeutic effect, while immunotherapy targeting the glioma microenvironment has offered a novel therapeutic option. PDIA5 protein is the member of PDI family, which is highly expressed in glioma and participates in glioma progression. Based on large-scale bioinformatics analysis, we discovered that PDIA5 expression level is upregulated in aggressive gliomas, with high PDIA5 expression predicting poor clinical outcomes. We also observed positive correlation between PDIA5 and immune infiltrating cells, immune related pathways, inflammatory activities, and other immune checkpoint members. Patients with high PDIA5 high-expression benefited from immunotherapies. Additionally, immunohistochemistry revealed that PDIA5 and macrophage biomarker CD68 were upregulated in high-grade gliomas, and patients with low PDIA5 level experienced favorable outcomes among 33 glioma patients. Single cell RNA sequencing exhibited that PDIA5 was in high level presenting in neoplastic cells and macrophages. Cell transfection and co-culture of glioma cells and macrophages revealed that PDIA5 in tumor cells mediated macrophages exhausting. Altogether, our findings indicate that PDIA5 overexpression is associated with immune infiltration in gliomas, and may be a promising therapeutic target for glioma immunotherapy.
Identifiants
pubmed: 33664747
doi: 10.3389/fimmu.2021.628966
pmc: PMC7921737
doi:
Substances chimiques
Biomarkers, Tumor
0
PDIA5 protein, human
EC 5.3.4.1
Protein Disulfide-Isomerases
EC 5.3.4.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
628966Informations de copyright
Copyright © 2021 Zhang, He, Dai, Wang, Liang, He, Xia, Feng, Cao, Zhang and Cheng.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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