Abstract
BackgroundThe prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear.MethodsA 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.ResultsBased 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).ConclusionsOur results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.
Highlights
The prognostic value of Pyruvate kinase isoform M2 (PKM2) and its correlation with tumour cell programmed death ligand 1 (PD-L1) in lung adenocarcinoma (LUAD) is unclear
Immunohistochemical analysis of lung adenocarcinoma tumour tissues showed that PKM2 was primarily expressed in the cytoplasm of tumour cells, whereas PD-L1 was expressed both on the membrane and in the cytoplasm of tumour cells (Fig. 1)
Considering that PD-L1 is mainly expressed on the cell surface, we only evaluated the membrane expression of PD-L1 and termed it tumour cells (TCs)-PD-L1
Summary
The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear. The identification of Pyruvate kinase isoform M2 (PKM2), a metabolic enzyme that catalyses the later steps of glycolysis, plays a key role in regulating metabolic activities in cancer cells and is necessary for tumour growth [6]. In addition to its known role as a metabolic enzyme, PKM2 can act as a signalling modulator in cancer development and progression [7, 8]. We identified that elevated expression of PKM2 is involved in cell proliferation and tumour formation in CD44+ A549 lung adenocarcinoma stem cells [9]. We found that enhanced PKM2 expression contributes to stress resistance and therapeutic resistance in CD44+ A549 lung adenocarcinoma stem cells, suggesting PKM2 as a potential target for lung adenocarcinoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
