Upregulated Expression of Pyruvate Kinase M2 MRNA Predicts Poor Prognosis in Lung Adenocarcinoma

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2020 Mar 3

PMID 32117639

Citations 1

Authors

Guiping Wang

Yingying Zhong

Jiecong Liang

Zhibin Li

Yun Ye

Affiliations

Soon will be listed here.

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.

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References

Saito M, Suzuki H, Kono K, Takenoshita S, Kohno T . Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy. Surg Today. 2017; 48(1):1-8. DOI: 10.1007/s00595-017-1497-7. View

Desai S, Ding M, Wang B, Lu Z, Zhao Q, Shaw K . Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers. Oncotarget. 2013; 5(18):8202-10. PMC: 4226677. DOI: 10.18632/oncotarget.1159. View

Mizuno H, Kitada K, Nakai K, Sarai A . PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009; 2:18. PMC: 2689870. DOI: 10.1186/1755-8794-2-18. View

Chu B, Wang J, Wang Y, Yang G . Knockdown of PKM2 induces apoptosis and autophagy in human A549 alveolar adenocarcinoma cells. Mol Med Rep. 2015; 12(3):4358-4363. DOI: 10.3892/mmr.2015.3943. View

Kobierzycki C, Pula B, Werynska B, Piotrowska A, Muszczynska-Bernhard B, Dziegiel P . The lack of evidence for correlation of pyruvate kinase M2 expression with tumor grade in non-small cell lung cancer. Anticancer Res. 2014; 34(7):3811-7. View

Gyorffy B, Surowiak P, Budczies J, Lanczky A . Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One. 2013; 8(12):e82241. PMC: 3867325. DOI: 10.1371/journal.pone.0082241. View

Sun H, Zhu A, Zhang L, Zhang J, Zhong Z, Wang F . Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma. Int J Mol Sci. 2015; 16(10):24574-87. PMC: 4632765. DOI: 10.3390/ijms161024574. View

Beer D, Kardia S, Huang C, Giordano T, Levin A, Misek D . Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 2002; 8(8):816-24. DOI: 10.1038/nm733. View

Wang Y, Deng H, Xin S, Zhang K, Shi R, Bao X . Prognostic and Predictive Value of Three DNA Methylation Signatures in Lung Adenocarcinoma. Front Genet. 2019; 10:349. PMC: 6492637. DOI: 10.3389/fgene.2019.00349. View

10.

Saito M, Shiraishi K, Kunitoh H, Takenoshita S, Yokota J, Kohno T . Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci. 2016; 107(6):713-20. PMC: 4968599. DOI: 10.1111/cas.12941. View

11.

Liu Z, Hong L, Fang S, Tan G, Huang P, Zeng Z . Overexpression of pyruvate kinase M2 predicts a poor prognosis for patients with osteosarcoma. Tumour Biol. 2016; 37(11):14923-14928. DOI: 10.1007/s13277-016-5401-7. View

12.

Stone O, El-Brolosy M, Wilhelm K, Liu X, Romao A, Grillo E . Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells. Nat Commun. 2018; 9(1):4077. PMC: 6177464. DOI: 10.1038/s41467-018-06406-8. View

13.

Cai L, Bai H, Duan J, Wang Z, Gao S, Wang D . Epigenetic alterations are associated with tumor mutation burden in non-small cell lung cancer. J Immunother Cancer. 2019; 7(1):198. PMC: 6660715. DOI: 10.1186/s40425-019-0660-7. View

14.

Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R . Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 2011; 72(1):100-11. DOI: 10.1158/0008-5472.CAN-11-1403. View

15.

Suzuki A, Puri S, Leland P, Puri A, Moudgil T, Fox B . Subcellular compartmentalization of PKM2 identifies anti-PKM2 therapy response in vitro and in vivo mouse model of human non-small-cell lung cancer. PLoS One. 2019; 14(5):e0217131. PMC: 6532891. DOI: 10.1371/journal.pone.0217131. View

16.

Papadaki C, Sfakianaki M, Lagoudaki E, Giagkas G, Ioannidis G, Trypaki M . PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer. Br J Cancer. 2014; 111(9):1757-64. PMC: 4453739. DOI: 10.1038/bjc.2014.492. View

17.

Hou J, Aerts J, den Hamer B, van IJcken W, den Bakker M, Riegman P . Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One. 2010; 5(4):e10312. PMC: 2858668. DOI: 10.1371/journal.pone.0010312. View

18.

Huang W, Hsu S, Huang H, Sun Y, Chou C, Weng S . MethHC: a database of DNA methylation and gene expression in human cancer. Nucleic Acids Res. 2014; 43(Database issue):D856-61. PMC: 4383953. DOI: 10.1093/nar/gku1151. View

19.

Vander Heiden M, Cantley L, Thompson C . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-33. PMC: 2849637. DOI: 10.1126/science.1160809. View

20.

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View