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

Abstract

Background: Protein disulfide isomerase (PDI) family mediates various biological functions. However, the gene family exert different effects on tumorigenesis and glioma development. The present study focused on the expression patterns, prognostic values and potential mechanism of the PDI family in gliomas. Methods: 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. Analysis of the distinctive genomic alterations in gliomas was achieved using published data of somatic mutation and copy number variation profiles. GSVA analysis revealed the underlying mechanisms of PDIs in gliomas. A novel clinical prognosis model was established via nomogram and ROC. qRT-PCR and immunohistochemistry validated the mRNA and protein expression patterns of the PDI genes respectively. Results: Most PDI family members' mRNA expressions were observed significantly different between gliomas classified by clinical features. High values of PDI signature/ risk score and cluster 1 in gliomas were associated with malignant clinicopathological characteristics and poor prognosis. Genomic alterations analysis 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. Conclusions: This research highlighted the clinical importance of PDI family in tumorigenesis and progression in gliomas. Funding Statement: This research was supported by the National Natural Science Foundation of China (NO.81703622), China Postdoctoral Science Foundation (NO. 2018M633002), Hunan Provincial Natural Science Foundation of China (NO.2018JJ3838), Foundation of Health Commission of Hunan Province of China (C2019186), and the Key Project of The Second People’s Hospital of Hunan Province (2018A06). Declaration of Interests: The authors declare that there are no potential conflicts of interest. Ethics Approval Statement: Not required.