CTHRC1在不同类型胶质瘤中的表达、预后价值及生物学功能：生物信息学分析与实验验证

Expression, Prognostic Value, and Biological Function of CTHRC1 in Different Types of Gliomas: A Bioinformatic Analysis and Experiment Validation.

作者信息

Shi Xueping, Zeng Xi, Jiao Rukai, Yang Yushi, Du Xiaolin, Qian Jiacai, Liu Jian, Chen Guangtang

机构信息

Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, P.R. China.

Department of Neurosurgery, The Jinyang Hospital Affiliated to Guizhou Medical University, Guiyang, P.R. China.

出版信息

Clin Med Insights Oncol. 2024 Jun 17;18:11795549241260576. doi: 10.1177/11795549241260576. eCollection 2024.

DOI:10.1177/11795549241260576

PMID:38894702

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11185027/

Abstract

BACKGROUND

In recent years, abnormal expression of collagen triple helix repeat containing 1 (CTHRC1) has been found in some tumors, closely related to the poor prognosis of cancer patients. However, the clinical significance of CTHRC1 in gliomas is not completely understood.

METHODS

We investigated the expression, prognostic value, and potential biological function of CTHRC1 in different types of gliomas through bioinformatics analysis and experimental verification.

RESULTS

Bioinformatics analysis revealed several key findings regarding the expression and clinical significance of CTHRC1 in gliomas. First, the analysis demonstrated a positive correlation between CTHRC1 expression and the World Health Organization (WHO) grading of gliomas, a relationship that was validated through immunohistochemistry experiments. In addition, a trend was observed in which CTHRC1 expression increased with the extent of glioma invasion, as supported by Western blot experiments. Subsequent bioinformatics analysis identified the mesenchymal subtype of gliomas as having the highest levels of CTHRC1 expression, a finding reinforced by immunohistochemical staining. Moreover, high CTHRC1 expression was associated with poor prognosis in gliomas and emerged as an independent prognostic factor, with varying impacts on prognosis between low-grade gliomas (LGGs) and glioblastoma (GBM) subgroups. Notably, comparative analysis unveiled distinct patterns of immune infiltration of CTHRC1 in LGG and GBM. Furthermore, alterations in copy number variations and DNA methylation were identified as potential mechanisms underlying elevated CTHRC1 levels in gliomas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that CTHRC1 and its associated genes mainly function in the extracellular matrix and participate in tumor-related signaling pathways.

CONCLUSIONS

The CTHRC1 has shown significant clinical utility as a prognostic marker and mesenchymal subtype marker of glioma.

摘要

背景

近年来，在一些肿瘤中发现含胶原三螺旋重复序列1（CTHRC1）表达异常，这与癌症患者的不良预后密切相关。然而，CTHRC1在胶质瘤中的临床意义尚未完全明确。

方法

我们通过生物信息学分析和实验验证，研究了CTHRC1在不同类型胶质瘤中的表达、预后价值及潜在生物学功能。

结果

生物信息学分析揭示了CTHRC1在胶质瘤中的表达及临床意义的几个关键发现。首先，分析表明CTHRC1表达与世界卫生组织（WHO）胶质瘤分级呈正相关，这一关系通过免疫组织化学实验得到验证。此外，蛋白质印迹实验支持了CTHRC1表达随胶质瘤侵袭程度增加的趋势。随后的生物信息学分析确定胶质瘤的间充质亚型CTHRC1表达水平最高，免疫组织化学染色进一步证实了这一发现。此外，CTHRC1高表达与胶质瘤预后不良相关，并成为独立的预后因素，对低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）亚组的预后影响不同。值得注意的是，比较分析揭示了CTHRC1在LGG和GBM中不同的免疫浸润模式。此外，拷贝数变异和DNA甲基化改变被确定为胶质瘤中CTHRC1水平升高的潜在机制。基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，CTHRC1及其相关基因主要在细胞外基质中发挥作用，并参与肿瘤相关信号通路。