Researchers at Baylor College of Medicine, Texas Children's Hospital, and other institutions have published new findings on Mar. 16 about a rare category of liver tumors in children known as hepatoblastoma with carcinoma features (HBC). The study, released in the Journal of Hepatology, provides detailed insight into the cellular makeup and development of these tumors.
The research is significant because HBC tumors display characteristics of both main types of pediatric liver cancer—hepatoblastoma (HB) and hepatocellular carcinoma (HCC)—and are associated with poorer survival rates compared to typical HB cases. Understanding how these tumors form and respond to treatment could help improve outcomes for affected children.
"In 2022, our team identified HBCs as a third group of liver tumor types in children," said Dr. Pavel Sumazin, professor of pediatrics, hematology-oncology at Baylor. Sumazin explained that the current study used multiple genetic profiling techniques to analyze 42 HBC samples, mapping out their cellular origins and responses to therapy. Using DNA and RNA single-cell sequencing, the researchers found that HBC tumors contain three kinds of cancer cells: HB-like cells, HCC-like cells, and unique HBC-specific cells with molecular features from both groups. "HBCs originate from hepatic stem cells and these types of undifferentiated tumor cells are less responsive to chemotherapy and immunotherapy," Sumazin said.
Analysis of treatment data from 41 patients showed that children with HBC had worse survival rates than those with typical HB. "The 5-year overall survival is about 80% for HB patients and around 40% for HBC patients overall, but transplanted HBC patients do better," Sumazin said. He added that this difference highlights the need to understand why HBC tumors resist standard treatments.
Further investigation revealed that HBC cells develop from HB progenitors and can transition toward an HCC state during early embryonic stages. "These transitions (HB → HBC → HCC) occur during early embryonic stages of liver development," Sumazin said. He noted that malfunctioning WNT signaling—a pathway important in normal liver development—prevents proper cell differentiation in all observed HBC cases. "But in all HBC tumors, WNT stays active and prevents cells from developing normally. Inhibiting WNT signaling promoted cell differentiation and enhanced sensitivity to chemotherapy," he said.
The study concludes that multiple independent transitions from HB to HBC occur within each tumor rather than arising from a single progenitor cell type. This dynamic process contributes to tumor diversity and impacts patient outcomes by linking sustained WNT signaling during early development to resistance against therapies.
