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丙酮酸激酶M2 mRNA表达上调预示肺腺癌预后不良。

Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma.

作者信息

Wang Guiping, Zhong Yingying, Liang Jiecong, Li Zhibin, Ye Yun

机构信息

Department of Pharmacy, Guangzhou Health Science College, Guangzhou, China.

College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou, China.

出版信息

PeerJ. 2020 Feb 20;8:e8625. doi: 10.7717/peerj.8625. eCollection 2020.

Abstract

BACKGROUND

Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis.

METHODS

Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan-Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database.

RESULTS

Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS ( = 2.80e-14), PPS ( = 0.022), FP ( = 1.30e-6) and RFS ( = 3.41e-8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs).

CONCLUSION

This study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.

摘要

背景

丙酮酸激酶M2(PKM2)是促成瓦伯格效应的关键调节因子。然而,PKM2在肺腺癌(LUAD)中的表达模式和预后价值仍不清楚。本研究的目的是通过综合生物信息学分析阐明PKM2的预后价值。

方法

首先,使用ONCOMINE和TCGA数据库系统分析LUAD中PKM2的mRNA表达水平。然后,通过UALCAN研究PKM2表达与临床参数之间的关联。使用Kaplan-Meier Plotter评估PKM2的预后意义。最后,使用MEXPRESS和MethHC数据库评估PKM2表达与其基因和表观遗传变化之间的关系。

结果

汇总分析表明,PKM2在LUAD中经常上调表达。随后,发现PKM2表达与肿瘤分期和淋巴结转移呈正相关,并且与较差的总生存期(= 2.80e-14)、无进展生存期(= 0.022)、无复发生存期(= 1.30e-6)和无病生存期(= 3.41e-8)也密切相关。重要的是,我们的结果表明,PKM2过表达与PKM2低甲基化和拷贝数变异(CNV)相关。

结论

本研究证实,LUAD中PKM2过表达与预后不良相关,提示PKM2可能作为LUAD一个有前景的预后生物标志物和新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ad6/7036274/ec8e2aacf943/peerj-08-8625-g001.jpg

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