羧肽酶Q及其甲基化在胶质母细胞瘤中的预后意义

Prognostic significance of carboxypeptidase Q and its methylation in glioblastoma.

作者信息

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

机构信息

Cancer Center, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Department of Radiation Oncology, People's Hospital of Zhongshan City, Zhongshan, China.

出版信息

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

DOI:10.21037/tcr-22-2562

PMID:37304538

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10248580/

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.

摘要

背景

胶质母细胞瘤（GBM）是一种侵袭性很强的颅内恶性肿瘤。羧肽酶Q（CPQ）在GBM中的作用尚不清楚。本研究旨在探讨CPQ及其甲基化在GBM中的预后意义。

方法

我们从癌症基因组图谱（TCGA）-GBM数据库收集数据，分析CPQ在GBM组织和正常组织中的差异表达。然后我们探讨了CPQ mRNA表达与DNA甲基化的相关性，并基于来自TCGA、中国胶质瘤基因组图谱（CGGA）和基因表达综合数据库（GEO）的另外六个数据集证实了它们的预后意义。利用基因本体分析和京都基因与基因组百科全书分析来研究CPQ在GBM中的生物学功能。此外，我们使用不同的生物信息学算法确定了CPQ表达与免疫细胞浸润、免疫标志物和肿瘤微环境的关联。使用R（版本4.1）和GraphPad Prism（版本8.0）分析数据。

结果

GBM组织中CPQ mRNA表达明显高于正常脑组织。CPQ的DNA甲基化与其表达呈负相关。CPQ表达低或甲基化水平高的患者总生存期（OS）明显更好。CPQ高表达和低表达患者之间差异表达基因相关的前20个生物学过程几乎都与免疫有关。差异表达基因涉及多个免疫相关信号通路。CPQ mRNA表达与CD8 T细胞、中性粒细胞、巨噬细胞和树突状细胞（DC）浸润显著相关。此外，CPQ表达与ESTIMATE评分和几乎所有免疫调节基因有显著关联。