The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma.

Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Gene Expression Regulation, Neoplastic*; Adenocarcinoma of Lung/*metabolism ; B7-H1 Antigen/*genetics ; Carrier Proteins/*metabolism ; Lung Neoplasms/*metabolism ; Membrane Proteins/*metabolism ; Thyroid Hormones/*metabolism; Adenocarcinoma of Lung/drug therapy ; Adult ; Aged ; B7-H1 Antigen/analysis ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Carrier Proteins/analysis ; Carrier Proteins/genetics ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms/drug therapy ; Male ; Membrane Proteins/analysis ; Membrane Proteins/genetics ; Middle Aged ; Proportional Hazards Models ; Thyroid Hormones/analysis ; Thyroid Hormones/genetics ; Thyroid Hormone-Binding Proteins

Background: The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear.
Methods: A total of 506 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) dataset and 173 LUAD tumour tissues from Jiangxi Cancer Hospital were used to analyse the correlation between PKM2 and PD-L1 expression. We further established a stable LUAD cell line with PKM2 knockdown and confirmed the association via Western blotting and flow cytometry analysis. Moreover, the prognostic values of PKM2 and PD-L1 were evaluated by the Kaplan-Meier method and Cox proportional hazards models.
Results: Based on the above two large cohorts, we found that PKM2 was significantly positively associated with PD-L1 expression (r = 0.132, P = 0.003 and r = 0.287, P < 0.001, respectively). Subsequently, we found that PKM2 knockdown substantially inhibited PD-L1 expression in the A549 LUAD cell line. Moreover, survival analysis showed that higher expression of PKM2 was correlated with significantly shorter overall survival (OS) and disease-free survival (DFS) in lung adenocarcinoma patients (P < 0.001 and P = 0.050, respectively). Subgroup analysis showed that lung adenocarcinoma patients who expressed high PKM2 and PD-L1 levels experienced the poorest OS and DFS. Additionally, multivariate analysis suggested that high PKM2 and PD-L1 expression was an independent prognostic indicator for worse OS and DFS (HR = 1.462, P < 0.001 and HR = 1.436, P = 0.004, respectively).
Conclusions: Our results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.

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81560382 National Natural Science Foundation of China; 20161BCB24011 Jiangxi Province's Program of the Preponderant Team Building in Science and Technology Innovation; 20181BBG70017 Key Research and Development Program of Jiangxi Province

Keywords: Lung adenocarcinoma; Prognostic factor; Programmed death ligand 1; Pyruvate kinase M2

0 (B7-H1 Antigen)
0 (Biomarkers, Tumor)
0 (CD274 protein, human)
0 (Carrier Proteins)
0 (Membrane Proteins)
0 (Thyroid Hormones)

Date Created: 20190331 Date Completed: 20190903 Latest Revision: 20231213

20240105

PMC6441172

10.1186/s12885-019-5519-2

30925904