Fig. 8

Expression of FBXO9 in lung cancer tissues and their association with patient survival A Comparison of FBXO9 mRNA expression between tumor and normal tissues by quantitative PCR using cDNA microarray (P < 0.0001). The bar graph shows significantly lower FBXO9 mRNA expression in tumor tissues (n = 15) compared to normal tissues (n = 15). B Analysis of GSE31210 dataset revealed a significant decrease in FBXO9 mRNA expression in lung cancer tissues (n = 113) compared to normal control tissues (n = 113) (P = 0.021). C Kaplan–Meier survival analysis of FBXO9 expression from GSE31210 dataset demonstrated that a higher level of FBXO9 mRNA was associated with a better overall survival (P = 0.004). D, E FBXO9 mRNA expression in lung cancer. Data analysis from TCGA database reveals that the mRNA expression of FBXO9 is notably downregulated in both LUAD (P = 0.0001) (D) and LUSC (P = 0.0007) (E) tissues when compared to their corresponding normal control tissues. F, G Prognostic value of FBXO9 mRNA expression in Lung Cancer. Data analysis from the TCGA database indicates that relatively lower expression of FBXO9 is associated with worse overall survival (OS) in lung cancer (P = 0.0006) (F). However, there is no significant difference in OS between patients with high and low expression of FBXO9 (P = 0.681) (G). H, I Protein expression of FBXO9 in LUAD. Immunohistochemistry (IHC) analysis on TAM samples (H) shows significantly lower FBXO9 levels in LUAD tissues compared to adjacent normal tissues (P < 0.001) (I). J Kaplan–Meier survival analysis of FBXO9 expression in TMA samples demonstrated that higher levels of FBXO9 protein correlated with improved overall survival (P = 0.004). K Representative images depicting the differential expression of FBXO9 protein in TMA samples. L FBXO9 controls lung cancer metastasis. A working model is as follows: In normal cells, FBXO9 promotes the ubiquitination of ATP6V1A, which helps maintain balanced cellular acidity by sequestering ATP6V1A in the cytoplasm and hindering V-ATPase assembly. However, in lung cancer cells, reduced FBXO9 levels disrupt ATP6V1A ubiquitination, leading to increased V-ATPase assembly and enhanced acidification of vesicles. The excessive acidification activates the Wnt signaling pathway and EMT, thereby driving the metastasis of lung cancer cells to distant sites. *P < 0.05, **P < 0.01, ***P < 0.001