CD147‐mediated glucose metabolic regulation contributes to the predictive role of ¹⁸F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

Abstract

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 18F‐fluorodeoxyglucose (18F‐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 18F‐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 18F‐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 18F‐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.

Glucose deprivation–induced aberrant FUT1-mediated fucosylation drives cancer stemness in hepatocellular carcinoma

“…The highly glycosylated form of CD147 has been shown to interact more with CD44 and EGFR to drive the Ras-MAPK signaling cascade than the low glycosylated form of CD147 (33). Glucose metabolism regulated by CD147 via an AKT-mTOR-dependent pathway has been reported in non-small cell lung cancer (34).…”

CD147 Expression Is Associated with Tumor Proliferation in Bladder Cancer via GSDMD

“…In addition, the promotion of CD147 in malignant neoplasms strongly depends on its cell surface presentation [8]. Although many studies have reported the role of CD147 in the promotion of tumor migration and invasion [9], proliferation [10], glucose metabolic regulation [11,12], immune escape [12], and confer resistance to chemotherapeutic drugs [13,14], there are only few studies that explore the clinicopathological correlation and prognostic relevance of CD147 in BC. e role of CD147 in the regulation of proliferation in BC should be fully elucidated.…”

Enhanced glucose metabolism mediated by CD147 is associated with 18F‐FDG PET/CT imaging in lung adenocarcinoma

“…18 The results from a study by Li et al provide in vitro and in vivo evidence that CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway significantly correlates with EGFR-TKI treatment sensitivity prediction in NSCLC using 18 F-FDG PET/CT imaging. 19 Nevertheless, there is no definitive clinical evidence which supports hat 18 F-FDG PET/CT imaging is associated with CD147 in LUAD. In the present study, we detected CD147 expression via IHC staining in a group of 70 LUAD tissues and analyzed the relationship between CD147 expression and PET metabolic parameters.…”

“…31 Several lines of previous studies have shown that CD147 is a crucial regulator of glucose metabolism in hepatocellular carcinoma (HCC), thyroid cancer (TC), and NSCLC. [17][18][19] According to Huang et al,17 CD147 significantly contributes to the reprogramming of glucose metabolism in HCC cells through a p53-dependent pathway, which suggests the pivotal role of CD147 in the process of tumor-associated glycolysis. Huang et al explored the molecular mechanisms that CD147 plays in TC, and their research indicated that miR-125a-5p regulates CD147, and through direct repression of the expression of the CD147 protein, miR-125a-5p suppresses aerobic glycolysis and lactate production and subsequently reduces TC cell viability, migration, and invasion, thereby exerting tumor suppressor functions.…”

“…Previous studies have shown that the silencing of CD147 dramatically decreases the glycolytic rate and lactate efflux in carcinoma cell lines, indicating the involvement of CD147 in tumor glycolysis. [17][18][19][20][21] However, the involvement of CD147 in reprogramming glucose metabolism in LUAD has not been well elucidated.…”