DUSP9 Regulates Hepatoblastoma Progression With Implications for Diagnosis and Targeted Therapy

ABSTRACT

This study investigated the mechanistic role of DUSP9 in hepatoblastoma (HB) development and progression to provide new insights into the diagnosis and treatment of pediatric HB. Pediatric HB mRNA expression data were obtained from the GEO database. Differentially expressed genes (DEGs) between patients with metastatic and non‐metastatic HB were analyzed using the R software, followed by a functional annotation of the DEGs. Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine‐Recursive Feature Elimination machine learning methods were employed to further screen for DEGs and identify DUSP9 as a key feature gene. The diagnostic efficacy of DUSP9 was evaluated using the area under the receiver operating characteristic curve. Additionally, in vitro and in vivo functional experiments were conducted to determine the effects of DUSP9 on HB progression. A total of 33 DEGs were identified. Gene Ontology analysis revealed that these DEGs were mainly associated with xenobiotics and fatty acid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis indicated involvement in regulating active transmembrane transporter activity and cytochrome P450‐mediated xenobiotic metabolism. Machine learning methods identified DUSP9 as a pivotal feature gene that was significantly upregulated in HB tumor tissues. In vitro functional assays demonstrated that DUSP9 knockdown markedly inhibited the proliferation and migration of HB cells. Additionally, western blot analysis revealed increased expression of epithelial markers and decreased expression of mesenchymal markers, along with a significant reduction in the phosphorylation of markers related to the MAPK signaling pathway. DUSP9 plays a crucial role in HB cell proliferation, migration, and epithelial–mesenchymal transition (EMT), potentially promoting tumor progression by regulating the MAPK signaling pathway.