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- W4384500291 abstract "Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children's health. Chemoresistance is the leading cause of mortality in HB patients. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need.We performed an integrative analysis including single-cell RNA sequencing, whole-exome sequencing, and bulk RNA sequencing in 180 HB samples, to reveal genomic features, transcriptomic profiles, and the immune microenvironment of HB. Multi-color immunohistochemistry staining and in vitro experiments were performed for validation. Here, we reported four HB transcriptional subtypes primarily defined by differential expression of transcription factors (TFs). Among them, the S2A subtype, characterized by strong expression of progenitor (MYCN, MIXL1) and mesenchymal TFs (TWIST1, TBX5), was defined as a new chemo-resistant subtype. The S2A subtype showed increased transforming growth factor beta (TGF-β) cancer-associated fibroblast and an immunosuppressive microenvironment induced by the upregulated TGF-β of HB. Interestingly, the S2A subtype enriched SBS24 signature and significantly higher serum aflatoxin B1-albumin (AFB1-ALB) level in comparison with other subtypes. Functional assays indicated that aflatoxin promotes hepatoblastoma to upregulate TGF-β. Furthermore, Clinical prognostic analysis showed that serum AFB1-ALB is a potential indicator of HB chemoresistance and prognosis.Our studies offer new insights into the relationship between aflatoxin and HB chemoresistance and provide important implications for its diagnosis and treatment." @default.
- W4384500291 created "2023-07-18" @default.
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- W4384500291 date "2023-07-17" @default.
- W4384500291 modified "2023-09-22" @default.
- W4384500291 title "A TGF-β-dominant chemo-resistant phenotype of hepatoblastoma associated with aflatoxin exposure in children" @default.
- W4384500291 doi "https://doi.org/10.1097/hep.0000000000000534" @default.
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- W4384500291 hasPublicationYear "2023" @default.
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