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PLOD1在恶性胶质瘤中的表达及预后作用

Expression and Prognostic Role of PLOD1 in Malignant Glioma.

作者信息

Wang Hao, Luo Weijian, Dai Limeng

机构信息

Department of Neurosurgery, Shenzhen People's Hospital (Second Clinical Medical College), Ji'nan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Dec 29;13:13285-13297. doi: 10.2147/OTT.S265866. eCollection 2020.

DOI:10.2147/OTT.S265866
PMID:33402837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7778385/
Abstract

BACKGROUND

Malignant glioma is rarely curable, and factors that influence the prognosis of glioma patients are not fully understood. Lysyl hydroxylases such as PLOD1 promote the cross-linking in extracellular matrix (ECM) molecules, which contribute to ECM structural stability and maturation. However, the expression and prognostic role of PLOD1 in malignant glioma remained to be determined.

METHODS

The expression of PLOD1 was evaluated by immunohistochemistry in 72 malignant glioma patients from Shenzhen People's hospital. The mRNA expression profiles and clinical information of malignant glioma patients were obtained from public databases, including TCGA, CGGA, Rembrandt, and Gravendeel. The correlation between gene expression and tumor grade, and IDH1/2 status and 1p19q status were evaluated. The association between gene expression and overall survival of malignant glioma patients was examined using Kaplan-Meier survival analysis. GO and KEGG pathways were analyzed by Metascape. Transwell invasion assays were performed to determine the effect of PLOD1 on migration and invasion of glioma cells in vitro.

RESULTS

PLOD1 expression was significantly elevated in malignant glioma tissues compared with non-tumor brain tissues. Besides, elevated levels of PLOD1 were significantly correlated with high tumor grade, wildtype IDH1/2 status, and 1p19q non-codel in all the four public datasets and in-house cohort. Malignant glioma patients with high PLOD1 expression had better overall survival compared to those with low PLOD1 expression. More importantly, patients with IDH1/2 mutations, 1p19q codeletions, and PLOD1 overexpression had the best overall survival. GO enrichment pathway analysis indicated that PLOD1 participates in regulating the extracellular matrix. Transwell invasion assay, which revealed that inhibiting PLOD1 reduced cell invasion in both U87 and U251 cells.

CONCLUSION

PLOD1 serves as a potential prognostic marker and therapeutic target for malignant glioma.

摘要

背景

恶性胶质瘤很少能治愈，影响胶质瘤患者预后的因素尚未完全明确。赖氨酰羟化酶如PLOD1可促进细胞外基质（ECM）分子的交联，这有助于ECM结构的稳定性和成熟。然而，PLOD1在恶性胶质瘤中的表达及预后作用仍有待确定。

方法

采用免疫组织化学法评估深圳市人民医院72例恶性胶质瘤患者中PLOD1的表达。恶性胶质瘤患者的mRNA表达谱和临床信息来自公共数据库，包括TCGA、CGGA、Rembrandt和Gravendeel。评估基因表达与肿瘤分级、IDH1/2状态和1p19q状态之间的相关性。采用Kaplan-Meier生存分析检验基因表达与恶性胶质瘤患者总生存期之间的关联。通过Metascape分析GO和KEGG通路。进行Transwell侵袭试验以确定PLOD1对胶质瘤细胞体外迁移和侵袭的影响。

结果

与非肿瘤脑组织相比，恶性胶质瘤组织中PLOD1表达显著升高。此外，在所有四个公共数据集和内部队列中，PLOD1水平升高与高肿瘤分级、野生型IDH1/2状态和1p19q非共缺失显著相关。PLOD1高表达的恶性胶质瘤患者总生存期优于PLOD1低表达患者。更重要的是，IDH1/2突变、1p19q缺失和PLOD1过表达的患者总生存期最佳。GO富集通路分析表明PLOD1参与调节细胞外基质。Transwell侵袭试验显示，抑制PLOD1可降低U87和U251细胞的侵袭能力。

结论

PLOD1可作为恶性胶质瘤潜在的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ee9/7778385/39f95f613772/OTT-13-13285-g0008.jpg
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