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

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

doi:10.7717/peerj.8625

Abstract

BackgroundPyruvate 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.MethodsFirstly, 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.ResultsPooled 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 (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs).ConclusionThis 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.

Highlights

Lung adenocarcinoma (LUAD), one of the most common malignant tumors worldwide, accounts for nearly 40∼50% of primary lung cancers
Transcriptional expression levels of Pyruvate kinase M2 (PKM2) in LUAC To address the mRNA expression of PKM2 in multiple human cancers, the expression of PKM2 in 20 different cancer types were assessed with ONCOMINE database
Relationship between PKM2 expression and clinical parameters in LUAC Subsequently, we explored the relationship between PKM2 expression and clinicopathological features, such as tumor stages, lymph node metastasis, smoking, gender, race and age in patients with LUAC

Summary

Introduction

Lung adenocarcinoma (LUAD), one of the most common malignant tumors worldwide, accounts for nearly 40∼50% of primary lung cancers. Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma. The expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). Methods: Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Results: Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). 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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