CD147-mediated glucose metabolic regulation contributes to the predictive role of F-FDG PET/CT imaging for EGFR-TKI treatment sensitivity in NSCLC.

The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using F-fluorodeoxyglucose ( F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD-L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR-TKI-sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote F-FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR-initiated Akt/mTOR-dependent signaling pathway. Programmed cell death-ligand 1 (PD-L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR-TKI treatment sensitivity prediction in NSCLC using F-FDG PET/CT imaging significantly correlated with CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway. Moreover, PD-L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.