HSPA6 is Correlated With the Malignant Progression and Immune Microenvironment of Gliomas.

Xiang Zhou,Weijun Wu,Feng Xiao,Qin Li,Min Luo,Minhua Ye,Li Lin,Qiankun Ji,Hua Guo,Guowen Hu,Yun Guo,Peng Wang,Kai Huang

doi:10.3389/fcell.2022.833938

Abstract

Gliomas are primary intracranial space lesions with a high mortality rate. Current treatments for glioma are very limited. Recently, immunotargeted therapy of the glioma microenvironment has been developed. Members of the 70 kDa heat shock protein (HSP70) family are involved in the development of many tumors and immunity. HSPA6 protein belongs to the HSP70 family; However, the biological function of this protein in gliomas has yet to be evaluated. In the present study, a range of analyses, involving protein networks, survival, clinical correlation, and function, revealed that the expression of HSPA6 was negatively correlated with clinical prognosis and closely associated with immunity, invasion, and angiogenesis. Quantitative protein analysis confirmed that HSPA6 was expressed at high levels in patients with glioblastoma. Vitro experiments further verified that HSPA6 enhanced the malignant progression of glioma cells by promoting proliferation, invasion and anti-apoptosis. We also found that HSPA6 was closely correlated with genomic variations and tumor microenvironment. Collectively, we demonstrated that HSPA6 may represent a new therapeutic target to improve the prognosis of patients with gliomas.

Highlights

Gliomas are derived from a group of neuroepithelial tumors that are collectively known as brain gliomas and account for the vast majority of primary brain tumors, the most common form of primary intracranial tumors (Ostrom et al, 2014)
According to the correlation score (Supplementary Table S3), the core network map showed that the core function of HSPA6 protein ranked sixth in the HSP70 family (Figure 2A)
We found several chaperone proteins of the BCL-2 associated athanogene (BAG) family that were associated with HSPA6 (Figure 2B)

Summary

Introduction

Gliomas are derived from a group of neuroepithelial tumors that are collectively known as brain gliomas and account for the vast majority of primary brain tumors, the most common form of primary intracranial tumors (Ostrom et al, 2014). The investigation of gene/protein regulatory networks and immunopathological mechanisms may identify novel molecular targeting and immunotherapeutic methods for glioma (Eckel-Passow et al, 2015). When heat shock proteins (HSPs) were first discovered in the salivary gland cells of drosophila in 1962 (Ritossa, 1962), they represent a widely distributed and highly conserved family of proteins that are usually expressed under a variety of physiological and stressful conditions, including carcinogenesis. HSP70 proteins are highly expressed in a wide range of malignant cancers and are negatively correlated with a poor clinical prognosis (Calderwood et al, 2006). Beaman et al (Beaman et al, 2014) proved that the expression of HSP70 genes and proteins were positively correlated with glioma grade. The mechanisms that mediate the effects of HSP70 family members on glioma remain unknown

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Discussion

Conclusion