Prognostic significance of carboxypeptidase Q and its methylation in glioblastoma

Qiaodan Liu; Rong Wang; Zizi Li; Yingpeng Peng; Wanling Qin; Xiao-Mou Peng; Zhi-Gang Liu

doi:10.21037/tcr-22-2562

Prognostic significance of carboxypeptidase Q and its methylation in glioblastoma

Transl Cancer Res. 2023 May 31;12(5):1073-1087. doi: 10.21037/tcr-22-2562. Epub 2023 May 23.

Authors

Qiaodan Liu^#¹, Rong Wang^#², Zizi Li^#³, Yingpeng Peng^#¹, Wanling Qin³, Xiao-Mou Peng⁴, Zhi-Gang Liu^{5

6}

Affiliations

¹ Cancer Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
² Department of Radiation Oncology, People's Hospital of Zhongshan City, Zhongshan, China.
³ Department of Pathology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
⁴ Center of Infectious Diseases, the Fifth affiliated hospital of Sun Yat-sen University, Zhuhai, China.
⁵ Cancer center, the Tenth Affiliated Hospital of Southern Medical University, Dongguan, China.
⁶ Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, Dongguan, China.

^# Contributed equally.

Abstract

Background: Glioblastoma (GBM) is a highly aggressive intracranial malignant tumor. The role of carboxypeptidase Q (CPQ) in GBM remains unknown. This study was to investigate the prognostic significance of CPQ and its methylation in GBM.

Methods: We collected data from The Cancer Genome Atlas (TCGA)-GBM database and analyzed the different expression of CPQ in GBM tissues and normal tissues. Then we explored the correlation of CPQ mRNA expression and DNA methylation, and confirmed the prognostic significance of them based on six additional datasets from TCGA, The Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) databases. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis were utilized to investigate the biological function of CPQ in GBM. Furthermore, we determined the association of CPQ expression and immune cell infiltration, immune markers and tumor microenvironment using different bioinformatic algorithms. R (version 4.1) and GraphPad Prism (version 8.0) were used to analyze the data.

Results: CPQ mRNA expression in GBM tissues was significantly higher than that in normal brain tissues. DNA methylation of CPQ was negatively correlated with its expression. Patients with low CPQ expression or higher CPQ methylation level had remarkably better overall survival (OS). The TOP20 biological processes relevant to the differentially expressed genes between high and low CPQ patients were almost all related to immunity. And the differentially expressed genes were involved in several immune-related signaling pathways. CPQ mRNA expression was outstandingly correlated with CD8⁺ T cells, neutrophils, macrophages and dendritic cell (DC) infiltration. Moreover, CPQ expression was meaningfully associated with the ESTIMATE score and almost all immunomodulatory genes.

Conclusions: Low CPQ expression and high methylation are associated with longer OS. CPQ is a promising biomarker for predicting prognosis in patients with GBM.

Keywords: Carboxypeptidase Q (CPQ); DNA methylation; glioblastoma (GBM); immune microenvironment; prognostic significance.