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(A) Representative IHC staining of CPT1a and CPT2 in the HB (tumour) and NT (non-tumour) regions (scale bar: 250 μm for 10× and 50 μm for 40×). (B) Bar graph showing expression of CPT1a and CPT2 in hepatoblastoma (T) and paired healthy liver tissue (NT) areas. ** p < 0.01. Five random areas from each tissue were quantified (means ± SEMs).
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Hepatoblastoma is a rare childhood liver cancer with poor outcomes for high-risk patients. Better treatments and better ways of identifying patients who respond poorly to treatment are needed. This paper uses new methods for identifying chemicals or metabolites produced in the tumour. By comparing the profiles of these metabolites in...
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... Reprogramming of cell metabolism has emerged as an important hallmark of cancer, increasing the tumor cells capability to sustain proliferation and invasion (Pavlova et al. 2022). Changes in metabolism have been increasingly described as important events in HBL in ours and other studies, although the complete landscape of alterations leading to this metabolic imbalance was not fully elucidated (Crippa et al. 2017;Rivas et al. 2020;Wang et al. 2020;Vastrad et al. 2020;Zhang et al. 2021;Tasic et al. 2022;Clavera-Cabello et al. 2023;Whitby et al. 2023). The observed downregulation of TTC36 in our data can be associated with alterations in the metabolism of amine and small molecules, development processes, and cell differentiation. ...
... This analysis revealed metabolites linked with altered metabolism in tumor tissues, such as phospholipids, triacyl glycerides, fatty acids, glucose, and amino acids. Later, Whitby et al. (2023) performed a metabolomic analysis on HBLs using liquid chromatography and tandem mass spectrometry (LC-MS/MS), observing a very similar pattern of metabolic imbalances. The assessment of these findings, together with the results of the present transcriptome analysis, strengthens that the disturbance of metabolic pathways is a major event in HBLs. ...
Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein–protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding RNAs (ncRNAs), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncRNAs. An integrative miRNA-mRNA analysis revealed crucial biological processes associated with metabolism, oxidation reactions of lipids and carbohydrates, and methylation-dependent chromatin silencing. In particular, four upregulated miRNAs (miR-186, miR-214, miR-377, and miR-494) played a pivotal role in the network, potentially targeting multiple protein-coding transcripts, including CCND1 and CAMK2B. In summary, our transcriptome analysis highlighted disrupted embryonic development as well as metabolic pathways, particularly those involving lipids, emphasizing the emerging role of ncRNAs as epigenetic regulators in hepatoblastomas. These findings provide insights into the complexity of the hepatoblastoma transcriptome and identify potential targets for future therapeutic interventions.
