Abstract
Background
Identifying effective biomarker in hepatoblastoma (HB) is important for predicting prognosis. This study committed to investigate the prognostic value of ferroptosis-related genes (FRGs) in HB.
Methods and Results
The two datasets of pediatric HB were obtained from Gene Expression Omnibus (GEO) database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WGCNA) was used to screen the key modules. FRGs were obtained from the ferroptosis database. Subsequently, after identified of the candidate hub genes by the intersection of DEGs, key module genes and FRGs, least absolute shrinkage and selection operator (LASSO) and receiver operating characteristic (ROC) curves were finally applied to identify the hub genes. Two hub genes, TRL4 and TUBE1, were obtained with the AUC of 0.940 and 0.932. The gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. The promoted expression of two hub genes in ferroptosis inducer, erastin-treated HB cell lines was verified via real-time qPCR. The effect of hub genes on viability and ferroptosis of HB cell line was verified in vitro. Specifically, the silence of TRL4 and TUBE1 could inhibit the ferroptosis and reverse the proliferation inhibition of HepG2 cells under erastin treating.
Conclusion
Ferroptosis-related genes TRL4 and TUBE1 emerge remarkable prognostic performance in pediatric HB as well as therapeutic target in the future. TRL4 and TUBE1 could function as tumor inhibiting factors in HB by promoting cell proliferation and prohibiting ferroptosis.