Phosphoenolpyruvate carboxykinase 2 Could Be Used For distiguishment Of Hepatoblastoma And Affecting Ferroptosis

Abstract

Hepatoblastoma (HB) is the most common malignant liver tumor in children, with low cure rates due to the lack of accurate predictive tar-gets. Phosphoenolpyruvate carboxykinase 2 (PCK2) has been implicated in various tumors and may regulate ferroptosis, but its role in HB remains unexplored. This study analyzed patient tissues and integrated mRNA microarray and RNA-seq data to assess PCK2 expression and its diagnostic value. Using GSE104462 and enrichment analysis of PCK2 differentially co-expressed genes (DCEGs), we also examined its association with ferroptosis-related genes. PCK2 expression was significantly downregulated in HB (pooled SMD = -1.93), with sequencing data confirming the result. PCK2 showed strong diagnostic performance (AUC = 0.99, sensitivity = 0.97, specificity = 0.98) in distinguishing HB from normal tissues. Enrichment analyses suggested PCK2 may regulate HB progression via the HIF-1 and Ras signaling pathways. Furthermore, PCK2 expression increased in HB cells treated with erastin and correlated with ferroptosis-related genes, indicating its potential involvement in ferroptosis. In conclusion, PCK2 demonstrates excellent diagnostic potential and may play a key role in ferroptosis-related pathways in HB.