PDIA4 Correlates with Poor Prognosis and is a Potential Biomarker in Glioma

Li, Haoyu; Liu, Qing; Xiao, Kai; He, Zhengxi; Wu, Chao; Sun, Jianjun; Chen, Xin; Chen, Suhua; Yang, Jun; Ma, Qianquan; Su, Jun

doi:10.2147/ott.s287931

Cited by 16 publications

(9 citation statements)

References 41 publications

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“…The P4HB (also known as PDIA1) and PDIA4, which were chosen from the six-gene signature, belong to the protein PDI protein family and have been proved to be related to ER stress activation in human cancers (Joo et al, 2007;Kranz et al, 2017;Winship et al, 2017;Liu et al, 2019;Wang et al, 2020), especially the PERK signaling pathway (Kranz et al, 2017(Kranz et al, , 2020. Serval recent researches has pointed out that P4HB and PDIA4 correlated with the malignant progression of glioma, but these conclusions have not been sufficiently verified by in vitro experiments (Zou et al, 2018;Li et al, 2021). Besides, the P4HB and PDIA4, which have significant prognostic value in gliomas, were also the important components of the ER stress-related signature.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

Huang

Wang

et al. 2021

Front. Cell Dev. Biol.

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BackgroundAs a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.MethodsA total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment in vitro were performed to explore the biological implication of this signature.ResultsWe found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.ConclusionThe ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

Huang

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…PDI family member PDIA4 has been shown to play roles in the pathogenesis of various diseases ( 4 ). Previous studies have uncovered the overexpression and cancer-promoting activity of PDIA4 in several types of cancer ( 6 , 7 , 9 ). In the present study, the expression pattern and biological roles of PDIA4 in cervical cancer were investigated.…”

Section: Discussionmentioning

confidence: 99%

“…PDIA4 exhibited a dramatic upregulation in docetaxel-resistant prostate cancer cells ( 9 ). Moreover, PDIA4 was an independent risk factor for disease-free survival and OS in ovarian cancer ( 29 ) and was associated with poor prognosis in patients with glioma ( 7 , 30 ). Recently, Wang et al ( 31 ) reported that PDIA4 could promote glioblastoma progression via the PI3K/AKT/mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

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High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer

2022

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The protein disulfide isomerase (PDI) gene family plays important roles in the maintenance of several cellular functions. Previous studies have showed that protein disulfide isomerase family A member 4 (PDIA4) is aberrantly expressed in several types of cancer, and correlates with prognosis of patients. However, the role of PDIA4 in cervical cancer remains unclear. In the present study, the expression pattern of PDIA4 from both public database and immunohistochemical analysis in cervical samples was analyzed. Cell Counting Kit-8 and Transwell assays were performed to determine the effect of PDIA4 on cervical cancer cell proliferation and migration. Gene set enrichment analysis (GSEA) was used to provide the associated enriched pathways of PDIA4 in regulating cervical tumorigenesis. It was observed that mRNA expression and protein level of PDIA4 were upregulated in cervical cancer tissues. High expression of PDIA4 was significantly associated with poor overall survival (P= 0.0095) and relapse-free survival (P= 0.0019) in The Cancer Genome Atlas cohort. Knockdown of PDIA4 inhibited cervical cancer cell proliferation and migration. Moreover, PDIA4 affected the expression of proliferation-related molecules (cyclin D1 and PCNA) and migration-related molecules (E-cadherin and Vimentin). Additionally, GSEA revealed that PDIA4 was significantly associated with gene signatures involving glycan biosynthesis, glycosaminoglycan degradation and protein export. In conclusion, the present findings highlighted the importance of PDIA4 in cervical oncogenesis, and suggested that targeting PDIA4 may be a potential therapeutic application for cervical cancer.

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“…Additionally, RIPK1/RIPK3 activation was proved to be correlated with the enhancement of antitumor immunity via maturated DC and CD8 + T cells in the tumor microenvironment (TME) ( Park et al, 2021 ). The necroptosis-related gene (NRG) PDIA4 was thought to be interrelated with glioma-related immune cells, such as CD8 + T cells, Tregs, and eosinophils ( Li et al, 2021 ). Previous research has proven that the mutants of isocitrate dehydrogenase 1 ( IDH1 ) can lead to necroptosis resistance by inducing hypermethylation of the RIPK3 promoter ( Yang et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing

Guo

Duan

Zhao

et al. 2022

Front. Mol. Biosci.

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Background: Glioma is the most fatal neoplasm among the primary intracranial cancers. Necroptosis, a form of programmed cell death, is correlated with tumor progression and immune response. But, the role of necroptosis-related genes (NRGs) in glioma has not been well-uncovered.Methods: Single-cell and bulk RNA sequencing data, obtained from publicly accessed databases, were used to establish a necroptosis-related gene signature for predicting the prognosis of glioma patients. Multiple bioinformatics algorithms were conducted to evaluate the efficacy of the signature. The relative mRNA level of each signature gene was validated by quantitative real-time reverse transcription PCR (qRT-PCR) in glioma cell lines compared to human astrocytes.Results: In this predicted prognosis model, patients with a high risk score showed a shorter overall survival, which was verified in the testing cohorts. The signature risk score was positively related with immune cell infiltration and some immune check points, such as CD276 (B7-H3), CD152 (CTLA-4), CD223 (LAG-3), and CD274 (PD-L1). Single-cell RNA sequencing analysis confirmed that the glioma microenvironment consists of various immune cells with different markers. The eight NRGs of the signature were detected to be expressed in several immune cells. QRT-PCR results verified that all the eight signature genes were differentially expressed between human astrocytes and glioma cells.Conclusion: The eight NRGs correlate with the immune microenvironment of glioma according to our bioinformatics analysis. This necroptosis-related gene signature may evaluate the precise methodology of predicting prognosis of glioma and provide a novel thought in glioma investigation.

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PDIA4 Correlates with Poor Prognosis and is a Potential Biomarker in Glioma

Cited by 16 publications

References 41 publications

Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

Comprehensive Analysis of the Clinical and Biological Significances of Endoplasmic Reticulum Stress in Diffuse Gliomas

High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing

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