Protein Disulfide Isomerases Are Promising Targets for Predicting the Survival and Tumor Progression in Glioma Patients

Peng, Zhigang; Chen, Yu; Cao, Hui; Zou, Hecun; Wan, Xin; Zeng, Wenjing; Liu, Yanling; Hu, Jiaqing; Zhang, Nan; Liu, Zhixiong; Cheng, Quan

doi:10.2139/ssrn.3449346

Cited by 12 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PDI family proteins are largely expressed in the endoplasmic reticulum (ER) ( 14 , 15 ), where they play an important regulatory role in protein homeostasis, but also may participate in tumor progression. Previous studies have shown that PDI family protein overexpression correlates with the occurrence, invasion, and metastasis of a variety of malignant tumors ( 16 – 20 ). Consequently, PDI family proteins are likely prognostic factors and therapeutic targets for related tumors ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, PDI family proteins are likely prognostic factors and therapeutic targets for related tumors ( 21 , 22 ). Two recent studies have demonstrated that the PDI family may serve as potential prognostic signature in gliomas ( 16 , 23 ), and PDIA6 ( 17 ), P4HB, and PDIA3 ( 24 ) have all been proven to be involved in glioma progression. Moreover, high P4HB level contributes significantly to temozolomide resistance ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

“…PDIA5 was first identified in 1995 and was found to be expressed in the brain, liver, kidney, and lungs ( 26 ). In gliomas, PDIA5 had significantly increased expression in gliomas compared with normal brain tissues ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas

Zhang

Dai

et al. 2021

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas

Zhang

Dai

et al. 2021

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lovat et al (26) demonstrated that overexpression of wild-type P4HB in melanoma cells decreased the level of apoptosis in response to ER stress, which was beneficial to the survival of tumor cells. Furthermore, recent studies have demonstrated that P4HB is overexpressed in gliomas and that P4HB suppression sensitizes glioblastoma to chemotherapy and radiotherapy by abrogating ER stress-induced UPR signaling (10,12,27). These results suggested the clinical importance of P4HB in tumorigenesis and progression.…”

Section: Term Description Fdrmentioning

confidence: 89%

P4HB: A novel diagnostic and prognostic biomarker for bladder carcinoma

Peng

Guan

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

Prolyl 4-hydroxylase, beta polypeptide (P4HB) protein is an endoplasmic reticulum (ER) molecular chaperone protein and has been reported to be overexpressed in multiple tumor types. However, the role of P4HB in bladder cancer (BLCA) has not yet been elucidated. The aim of the present study was to investigate the prognostic value of P4HB and the association between clinicopathological characteristics and P4HB in BLCA. P4HB expression levels were assessed through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis in BLCA tissues and cells. A total of 69 pairs of tumor and normal samples were used to analyze the expression of P4HB via immunohistochemical staining. A co-expression network and functional enrichment analyses were conducted to investigate the biological function of P4HB in BLCA. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes. The results showed that P4HB was highly expressed in BLCA cells and tissues. The area under the curve value for P4HB expression to discriminate between tumor and normal tissues was up to 0.888 (95% CI: 0.801–0.975; P<0.001) and 0.881 (95% CI: 0.825–0.937; P<0.001) in TCGA database and our database, respectively. Furthermore, the expression level of P4HB was an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) by univariate and multivariate analyses. Kaplan-Meier survival analysis demonstrated that high P4HB expression was associated with low OS and RFS. Pathway enrichment analysis suggested that P4HB was involved in protein processing in the endoplasmic reticulum (ER), including N-glycan modification and protein metabolic processes responding to ER stress. PPI analysis revealed that the potential targets of P4HB were mainly involved in posttranslational protein modification and response to ER stress. In conclusion, the expression level of P4HB aid in identifying patients with early-stage BLCA and predicting the prognosis of BLCA. Therefore, P4HB may be a novel diagnostic and prognostic biomarker for BLCA.

show abstract

“…As another important member in the TME, immune checkpoint molecules are also involved in immunosuppressive mechanism. Immunotherapy of immune checkpoint blockade has become a promising treatment modality for cancers ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Correlation Between APOBEC3B Expression and Clinical Characterization in Lower-Grade Gliomas

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundAs the most aggressive tumors in the central nervous system, gliomas have poor prognosis and limited therapy methods. Immunotherapy has become promising in the treatment of gliomas. Here, we explored the expression pattern of APOBEC3B, a genomic mutation inducer, in gliomas to assess its value as an immune biomarker and immunotherapeutic target.MethodsWe mined transcriptional data from two publicly available genomic datasets, TCGA and CGGA, to investigate the relevance between APOBEC3B and clinical characterizations including tumor classifications, patient prognosis, and immune infiltrating features in gliomas. We especially explored the correlation between APOBEC3B and tumor mutations. Samples from Xiangya cohort were used for immunohistochemistry staining.ResultsOur findings demonstrated that APOBEC3B expression level was relatively high in advanced gliomas and other cancer types, which indicated poorer prognosis. APOBEC3B also stratified patients’ survival in Xiangya cohort. APOBEC3B was significantly associated with infiltrating immune and stromal cell types in the tumor microenvironment. Notably, APOBEC3B was involved in tumor mutation and strongly correlated with the regulation of oncogenic genes.ConclusionOur findings identified that APOBEC3B could be a latent molecular target in gliomas.

show abstract

Protein Disulfide Isomerases Are Promising Targets for Predicting the Survival and Tumor Progression in Glioma Patients

Cited by 12 publications

References 0 publications

PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas

PDIA5 is Correlated With Immune Infiltration and Predicts Poor Prognosis in Gliomas

P4HB: A novel diagnostic and prognostic biomarker for bladder carcinoma

Correlation Between APOBEC3B Expression and Clinical Characterization in Lower-Grade Gliomas

Contact Info

Product

Resources

About