Pediatr Res. 2025 Nov 19. doi: 10.1038/s41390-025-04492-1. Online ahead of print.
ABSTRACT
BACKGROUND: Hepatoblastoma is the most common primary liver cancer in infants and children, with rising incidence worldwide over the past 30 years. Despite numerous advancements in understanding its genetic and epigenetic influences, a definitive etiology remains unidentified. This study investigates genetic signatures associated with hepatoblastoma, identifying potential causative mutations, therapeutic targets, and diagnostic biomarkers.
METHODS: STARGEO was utilized to identify 138 hepatoblastoma tumor samples and 41 healthy liver control samples. Meta-analysis was performed and associated gene signatures were analyzed using Ingenuity Pathway Analysis and restricted to genes with p < 0.05 and absolute experimental log ratio >0.2.
RESULTS: 2202 molecules showed significant differential expression between hepatoblastoma and healthy liver. Upregulated genes, largely involved in transcription regulation and Wnt signaling inhibition, include DKK1, WIF1, SLC7A11, CENPA, and HMGA2. Key pathways include selenoamino acid metabolism and cell cycle checkpoints.
CONCLUSIONS: This study highlights the role of Wnt signaling, metabolic changes, and liver dysfunction in hepatoblastoma. Therapeutic strategies targeting Wnt inhibition, ferroptosis induction, and cell cycle regulation warrant further investigation. While these findings provide valuable insights, further experimental validation is necessary to confirm causal relationships and therapeutic applicability. Identifying novel genetic signatures in hepatoblastoma is a foundational step to uncovering potential preventative strategies and developing targeted treatment.
IMPACT: This study investigates differentially expressed genes and pathways in hepatoblastoma, shedding light on disease mechanisms and identifying potential biomarkers for diagnosis and treatment. The findings highlight therapeutic strategies involving Wnt inhibition, ferroptosis induction, and cell cycle regulation, guiding future research into innovative treatment modalities for hepatoblastoma. Key genes CENPA, HMGA2, WIF1, DKK1, and SLC7A11 warrant further investigation due to their potential implications in hepatoblastoma tumorigenesis and proliferation. This study expands the current understanding of genetic influences of hepatoblastoma and informs future research into drivers of hepatoblastoma pathogenesis by leveraging a novel approach utilizing publicly available data.
PMID:41261163 | DOI:10.1038/s41390-025-04492-1
