Clusterin Is a Prognostic Biomarker of Lower-Grade Gliomas and Is Associated with Immune Cell Infiltration

Xiaoyue Ren; Chao Chang; Teng Qi; Pengyu Yang; Yuanbo Wang; Xiaorui Zhou; Feng Guan; Xiang Li

doi:10.3390/ijms241713413

Clusterin Is a Prognostic Biomarker of Lower-Grade Gliomas and Is Associated with Immune Cell Infiltration

Int J Mol Sci. 2023 Aug 29;24(17):13413. doi: 10.3390/ijms241713413.

Authors

Xiaoyue Ren¹, Chao Chang¹, Teng Qi¹, Pengyu Yang¹, Yuanbo Wang¹, Xiaorui Zhou¹, Feng Guan², Xiang Li^{1

3}

Affiliations

¹ Provincial Key Laboratory of Biotechnology, Institute of Hematology, School of Medicine, Northwest University, Xi'an 710069, China.
² Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an 710069, China.
³ College of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an 710069, China.

Abstract

Dysregulation of clusterin (CLU) has been demonstrated in many cancers and has been proposed as a regulator of carcinogenesis. However, the roles of CLU in gliomas remain unclear. The expression of CLU was assessed using TIMER2.0, GEPIA2, and R package 4.2.1 software, leveraging data from TCGA and/or GTEx databases. Survival analysis and Cox regression were employed to investigate the prognostic significance of CLU. Immune infiltration was evaluated utilizing TIMER2.0, ESTIMATE, and CIBERSORT. The findings reveal the dysregulated expression of CLU in many cancers, with a marked increase observed in glioblastoma and lower-grade glioma (LGG). High CLU expression indicated worse survival outcomes and was an independent risk factor for the prognosis in LGG patients. CLU was involved in immune status as evidenced by its strong correlations with immune and stromal scores and the infiltration levels of multiple immune cells. Additionally, CLU was co-expressed with multiple immune-related genes, and high CLU expression was associated with the activation of immune-related pathways, such as binding to the antigen/immunoglobulin receptor and aiding the cytokine and cytokine receptor interaction. In conclusion, CLU appears to play crucial roles in tumor immunity within gliomas, highlighting its potential as a biomarker or target in glioma immunotherapy.

Keywords: clusterin; glioma; immune infiltration; prognostic.

MeSH terms

Carcinogenesis
Clusterin / genetics
Glioblastoma*
Glioma* / genetics
Humans
Prognosis

Substances

Clusterin
CLU protein, human

Grants and funding

This study was supported by the National Science Foundation of China (No. 32071274, 82100148, 31971211), Science Foundation for Distinguished Young Scholars of Shaanxi Province (2021JC-39), the Natural Science Foundation of Shaanxi Province (2021SF-294), and the Youth Innovation Team of Shaanxi Universities.