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P4HB and PDIA3 are associated with tumor progression and therapeutic outcome of diffuse gliomas
Hecun Zou1, Chunjie Wen1, Zhigang Peng2
1Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, P.R. China.
Abstract:
Diffuse gliomas are the most common type of primary brain and central nervous system (CNS) tumors. Protein disulfide isomerases (PDIs) such as P4HB and PDIA3 act as molecular chaperones for reconstructing misfolded proteins, and are involved in endoplasmic reticulum stress and the unfolded protein response. The present study focused on the role of P4HB and PDIA3 in diffuse gliomas. Analysis of GEO and HPA data revealed that the expression levels of P4HB and PDIA3 were upregulated in glioma datasets. their increased expression was then validated in 99 glioma specimens compared with 11 non-tumor tissues. High expression of P4HB and PDIA3 was significantly correlated with high Ki-67 and a high frequency of the TP53 mutation. Kaplan-Meier survival curve and Cox regression analyses showed that glioma patients with high P4HB and PDIA3 expression had a poor survival outcome, P4HB and PDIA3 could be independent prognostic biomarkers for diffuse gliomas. In vitro, knockdown of PDIA3 suppressed cell proliferation, induced cell apoptosis, and decreased the migration of glioma cells. Furthermore, downregulation of P4HB and PDIA3 may contribute to improve the survival of patients who receive chemotherapy and radiotherapy. The data suggest that high expression of P4HB and PDIA3 plays an important role in glioma progression, and could predict the survival outcome and therapeutic response of glioma patients. Therefore, protein disulfide isomerases may be explored as prognostic biomarkers and therapeutic targets for diffuse gliomas.
Insights
High expression of protein disulfide isomerases (PDIs), P4HB and PDIA3, correlates with diffuse glioma progression and poor survival. Targeting these PDIs may improve patient outcomes and therapeutic responses.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Diffuse gliomas are common primary brain tumors.
- Protein disulfide isomerases (PDIs) like P4HB and PDIA3 are involved in protein folding and cellular stress.
- Their role in diffuse gliomas requires further investigation.
Purpose of the Study:
- To investigate the role of P4HB and PDIA3 in diffuse glioma progression.
- To evaluate P4HB and PDIA3 as prognostic biomarkers for diffuse gliomas.
- To explore P4HB and PDIA3 as potential therapeutic targets.
Main Methods:
- Analysis of GEO and HPA datasets for P4HB and PDIA3 expression.
- Validation of expression in 99 glioma and 11 non-tumor tissues.
- Correlation analysis with clinical parameters (Ki-67, TP53 mutation) and survival data (Kaplan-Meier, Cox regression).
- In vitro knockdown experiments for PDIA3 function.
Main Results:
- P4HB and PDIA3 expression were significantly upregulated in diffuse gliomas.
- High P4HB/PDIA3 expression correlated with increased Ki-67, TP53 mutation frequency, and poor patient survival.
- PDIA3 knockdown inhibited glioma cell proliferation and migration, and induced apoptosis.
- Downregulation of P4HB and PDIA3 may enhance response to chemotherapy and radiotherapy.
Conclusions:
- P4HB and PDIA3 are significantly associated with diffuse glioma progression and serve as independent prognostic biomarkers.
- Targeting P4HB and PDIA3 could offer a novel therapeutic strategy for diffuse gliomas.
- These PDIs may predict patient survival and response to standard therapies.
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