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

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

doi:10.2147/OTT.S287931

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

Onco Targets Ther. 2021 Jan 8:14:125-138. doi: 10.2147/OTT.S287931. eCollection 2021.

Authors

Haoyu Li¹, Qing Liu¹, Kai Xiao¹, Zhengxi He², Chao Wu³, Jianjun Sun³, Xin Chen³, Suhua Chen³, Jun Yang³, Qianquan Ma³, Jun Su⁴

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People's Republic of China.
² Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People's Republic of China.
³ Department of Neurosurgery, Peking University Third Hospital, Peking University, Beijing 100191, People's Republic of China.
⁴ Department of Neurosurgery, Hunan Children's Hospital, Changsha 410007, Hunan, People's Republic of China.

Abstract

Purpose: Gliomas, characterized by aggressiveness and invasiveness, remain incurable after conventional therapies. The molecular mechanisms driving the progression and maintenance of glioma are still poorly understood.

Methods: The TCGA and CGGA databases were chosen for bioinformatics analysis. Gene expression profiling interactive analysis (GEPIA) was performed for differential analysis. The Kaplan-Meier method was chosen for survival analysis. Analysis of stromal and immune infiltration was performed using the ESTIMATE algorithm and xCell package. qPCR and Western blotting were performed to measure the expression of PDIA4 at the mRNA and protein levels. IHC was performed to detect the expression of PDIA4 in glioma tissues. The viability of glioma cells was evaluated by the CCK8 assay.

Results: In this study, we identified high PDIA4 expression in gliomas that correlated with poor prognosis. The association between IDH1 and different glioma patterns also indicated the potential biological role of PDIA4 in tumor development. Mechanistically, PDIA4 interacted with multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Knockdown of PDIA4 significantly impaired the proliferation of GBM cells.

Conclusion: Our results confirm that PDIA4 is an efficient biomarker of gliomas, with clinical implications for prognosis and therapeutic strategies.

Keywords: PDIA4; biomarker; glioma; immune cells; prognosis.

Grants and funding

The study was supported by “National Natural Science Foundation of China” (Grant Number: 81872051) and the “Peking University Clinical Scientist Program” (Grant Number: BMU2019LCKXJ007).