High Level of Component C1q Binding Protein (C1QBP) is Associated With Poor Prognosis and Dysfunction of Mast Cells in Lung Adenocarcinoma

BACKGROUND: Component C1q binding protein (C1QBP) is known as an important regulator of mitochondrial plasticity and is involved in antitumor immune response in cancers. Nevertheless, its role in lung adenocarcinoma (LUAD) still remains largely unknown. METHODS: C1QBP expression in LUAD and adjacent normal samples was compared by Wilcoxon test, and the corresponding receiver operating characteristic (ROC) curve was used to estimate its diagnostic value. Associations between C1QBP expression levels and different clinical traits were analyzed by chi-square test; K-M curves were applied for analyzing survival differences, and univariate and multivariate Cox analysis were employed to construct the C1QBP-related nomogram model. Furthermore, GSEA and immune analysis were performed to explore the mechanism. Finally, rhC1QBP was applied to cultured mast cells in vivo to investigate its regulatory effect on mast cell dysfunction, and sh-C1QBP was injected into LUAD xenograft mice to explore the effect of C1QBP knockdown on tumor growth in vivo. RESULTS: The C1QBP expression level, with a preferable diagnosis effect, was significantly different between LUAD and normal samples, and was notably interrelated with gender, TNM stage, and Fustat in LUAD patients. LUAD patients with high C1QBP levels displayed lower survival rates. Our nomogram based on C1QBP expression and T stage displayed decent prediction capability. There was a significant difference in C1QBP expression in plasma cells, regulatory T cells (Tregs), activated CD4 memory T cells, resting mast cells, and eosinophils between LUAD patients and the controls. Upregulation of C1QBP with rhC1QBP treatment promoted mast cell ferroptosis through interacting with the Cullin3 protein. While Fer-1, a ferroptosis inhibitor, counteracted rhC1QBP induced ferroptosis in mast cells. Knockdown of C1QBP inhibited tumor growth in xenograft mice. CONCLUSION: C1QBP may be a promising potential prognostic biomarker in LUAD and a potential therapeutic target by affecting the immune microenvironment of LUAD patients.