Protein disulfide isomerases are promising targets for predicting the survival and tumor progression in glioma patients.

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

doi:10.18632/aging.102748

Abstract

The present study focused on the expression patterns, prognostic values and potential mechanism of the PDI family in gliomas. Most PDI family members’ mRNA expressions were observed significantly different between gliomas classified by clinical features. Construction of the PDI signature, cluster and risk score models of glioma was done using GSVA, consensus clustering analysis, and LASSO Cox regression analysis respectively. High values of PDI signature/ risk score and cluster 1 in gliomas were associated with malignant clinicopathological characteristics and poor prognosis. Analysis of the distinctive genomic alterations in gliomas revealed that many cases having high PDI signature and risk score were associated with genomic aberrations of driver oncogenes. GSVA analysis showed that PDI family was involved in many signaling pathways in ERAD, apoptosis, and MHC class I among many more. Prognostic nomogram revealed that the risk score was a good prognosis indicator for gliomas. The qRT-PCR and immunohistochemistry confirmed that P4HB, PDIA4 and PDIA5 were overexpressed in gliomas. In summary, this research highlighted the clinical importance of PDI family in tumorigenesis and progression in gliomas.

Highlights

Gliomas are the most common brain and central nervous system (CNS) tumors
CBTRUS reported that the median age at diagnosis for GBM was 65 years and survival time was markedly reduced in the elderly patients [2]
Dorota et al showed that PDIA6 was over-expressed in migrating glioma cells and invasive glioma cells, indicating the important role PDIA6 plays in glioma invasion [19]

Summary

Introduction

Gliomas are the most common brain and central nervous system (CNS) tumors. According to cancer statistics, gliomas account for approximately 80% of all malignant primary brain tumors and 57.3% of gliomas was glioblastoma (GBM) [1, 2]. The Central Brain Tumor Registry of the United States (CBTRUS) statistical report revealed that the incidence rate of glioblastoma increased with age, with 1.24 per 100,000 population in age 35–44 years, 8.07 in age 55–64 years, 12.98 in age 65–74 years and with the highest rates in 75–84 years (15.29 per 100,000 population) [2]. After a safe surgical resection, GBM patients are treated with radiotherapy and chemotherapy [6] Their survival rate is very limited with most of the patients dying within 15–18 months post-diagnosis while just 6.8% of the patients survive up to five years [2, 7,8,9]. Glioblastoma is a major threat to human health, especially in the elderly

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Conclusion