학술논문

Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids
Document Type
article
Source
Nature Communications. 13(1)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Immunology
Pediatric Research Initiative
Pediatric
Cancer
Clinical Research
Digestive Diseases
Rare Diseases
Liver Disease
Pediatric Cancer
Good Health and Well Being
Chemotherapy
Adjuvant
Child
Hepatoblastoma
Humans
Infant
Liver Neoplasms
Precision Medicine
Single-Cell Analysis
Language
Abstract
Pediatric hepatoblastoma is the most common primary liver cancer in infants and children. Studies of hepatoblastoma that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, hepatoblastoma tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we use single-cell transcriptomic techniques to analyze resected human pediatric hepatoblastoma specimens, and identify five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease. Notably, patient-derived hepatoblastoma spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. In this work, we define hepatoblastoma tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.