A Novel Method for Observing Tumor Margin in Hepatoblastoma Based on Microstructure 3D Reconstruction.

Objective: We investigated three-dimensional (3 D) reconstruction for the assessment of the tumor margin microstructure of hepatoblastoma (HB). Methods: Eleven surgical resections of childhood hepatoblastomas obtained between September 2018 and December 2019 were formalin-fixed, paraffin-embedded, serially sectioned at 4 µm, stained with hematoxylin and eosin (every 19th and 20th section stained with alpha-fetoprotein and glypican 3), and the digital images of all sections were acquired at 100× followed by image registration using the B-spline based method with modified residual complexity. Reconstruction was performed using 3 D Slicer software. Results: The reconstructed orthogonal 3 D images clearly presented the internal microstructure of the tumor margin. The rendered 3 D image could be rotated at any angle. Conclusions: Microstructure 3 D reconstruction is feasible for observing the pathological structure of the HB tumor margin.

Trans-Ancestry Mutation Landscape of Hepatoblastoma Genomes in Children.

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children. The incidence rate varies among different populations. However, genetic differences in HB patients with different epidemiological and ancestral backgrounds have not been found. In this study, we aim to analyze data from 16 patients treated at our center and collected published data from whole-exome sequencing studies on HB, and to explore the genetic differences between races. Data from a total of 75 HB patients of three races (24 Asian, 37 Caucasian and 14 Hispanic) were analyzed. We identified 16 genes with recurrent somatic mutations and 7 core pathway modules. Among them, the Wnt/ß-catenin pathway had the highest mutation rate, and the mutation frequency in Caucasians and Hispanics was approximately twice as high as that in Asians. In addition, this study compared the characteristics of gene mutations between patients who underwent preoperative chemotherapy and those who did not and found that there was no significant difference in gene mutations between the two groups. We also preliminarily verified the function of cancer-associated candidate genes (CTNNB1 and KMT2D). In conclusion, we found ethnic differences in HB biology at the genomic level, which expands our understanding of the genetics of HB in children.

Identification of Potential Biomarkers of Prognosis-Related Long Non-Coding RNA (lncRNA) in Pediatric Rhabdoid Tumor of the Kidney Based on ceRNA Networks.

BACKGROUND Long non-coding RNA (lncRNA) can act as competing endogenous RNA (ceRNA) during tumor development. However, no study has elucidated the ceRNA network in pediatric rhabdoid tumor of the kidney (RTK) and its prognostic-related lncRNAs. The goal of the present study was to identify potential biomarkers of prognostic-related lncRNAs. MATERIAL AND METHODS RNA sequencing and clinical data were procured from the TARGET database. The "EdgeR" package was used to obtain differentially expressed lncRNA (DElncRNA), differentially expressed messenger RNAs (DEmRNA), and differentially expressed microRNAs (DEmiRNA). Cytoscape software was used to construct a ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted on the ceRNA network-related DEmRNA. The Kaplan-Meier method was used for predicting survival with ceRNA network-related DElncRNA. Univariate and multivariate Cox analyses were used to identify prognosis-related lncRNAs in the ceRNA network, and an RTK prognostic signature was constructed. RESULTS We identified 1109 DElncRNAs, 215 DEmiRNAs, and 3436 DEmRNAs; and 107 DElncRNAs, 21 DEmiRNAs, and 74 DEmRNAs were included in the ceRNA regulatory network. GO enrichment analysis and KEGG pathway enrichment indicated that the DEmRNAs were mainly related to the regulation of phospholipase C activity and the MAPK signaling pathway. Survival analysis showed that 9 of 107 DElncRNAs were correlated with prognosis (P<0.05). Univariate and multivariate Cox analysis identified 4 DElncRNAs (HNF1A-AS1, TPTEP1, SNHG6, and ZNF503-AS2) to establish a predictive model and can be used as independent prognostic biomarkers. CONCLUSIONS We constructed a ceRNA network that reveals potential lncRNA biomarkers for pediatric RTK.