COMMD4 is a novel prognostic biomarker and relates to potential drug resistance mechanism in glioma

Zongheng Liu; Long Peng; Yidan Sun; Zhichao Lu; Bing Wu; Weichen Wang; Xiaomei Zhang; Haiyan Hao; Peipei Gong

doi:10.3389/fphar.2022.974107

COMMD4 is a novel prognostic biomarker and relates to potential drug resistance mechanism in glioma

Front Pharmacol. 2022 Sep 30:13:974107. doi: 10.3389/fphar.2022.974107. eCollection 2022.

Authors

Zongheng Liu^{1

2}, Long Peng¹, Yidan Sun³, Zhichao Lu¹, Bing Wu^{1

2}, Weichen Wang¹, Xiaomei Zhang¹, Haiyan Hao⁴, Peipei Gong¹

Affiliations

¹ Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
² Postgraduate School, Dalian Medical University, Dalian, China.
³ Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
⁴ Department of Outpatient, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

Background: Glioma as the most frequently discovered tumor affecting the brain shows significant morbidity and fatality rates with unfavorable prognosis. There is an urgent need to find novel therapeutic targets to overcome the low chemotherapeutic efficacy of glioma. This research examined whether the copper-metabolism-domain protein, COMMD4, had predictive and therapeutic significance in glioma. Methods: Using the freely accessible CGGA (The Chinese Glioma Atlas) and TCGA (The Cancer Genome Atlas) databases, we examined the function of COMMD4 in GBM and LGG. CIBERSORT and TIMER were utilized to assess the associations between COMMD4 and immune cells. The Gene Set Enrichment Analysis (GSEA) was employed to examine the functional data. Furthermore, the link between COMMD4 expression and predicted treatment response was evaluated via CellMiner Cross-Database. Meanwhile, qRT-PCR was conducted to examine COMMD4 expression in human glioma. Finally, Migration and invasion of glioma cells (U-87, U-251) were assessed using transwell assays. R was used to analyze the statistical data. Results: According to our findings, COMMD4 expression level was higher in patients having grade-dependent glioma who also showed an unfavorable prognosis. Furthermore, qRT-PCR confirmed the high expression of COMMD4 in glioma tissues and cells. Additionally, using integrated correlation analysis, we acquired significant prognostic findings between isocitrate dehydrogenase 1(IDH1) and COMMD4. Meanwhile, a link between COMMD4 and many tumor-infiltrating immune cells was observed. GSEA and drug response analysis revealed the potential mechanism of COMMD4 in drug resistance of glioma. Conclusion: The current findings validated COMMD4 as a novel biological marker, which might offer insights into the possible drug resistance mechanisms and the impact of the immune microenvironment on glioma. COMMD4 might be used to predict glioma prognosis.

Keywords: CGGA; COMMD4; TCGA; drug resistance; glioma; mast cells.