1. Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma
- Author
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Jin-shu Pang, Yong Li, Yujia Zhao, Dong-Yue Wen, Rong-Quan He, Jia-Bo Chen, Linyong Wu, Gang Chen, Hong Yang, Jun-Hong Chen, Jin-Hong Li, Peng Lin, Yun He, and Li-Ting Qin
- Subjects
Hepatoblastoma ,Liver tumor ,Neoplasm, Residual ,Mice, Nude ,Bioengineering ,Malignancy ,Applied Microbiology and Biotechnology ,ablation ,Transcriptome ,Mice ,Nude mouse ,Recurrent Hepatoblastoma ,medicine ,Animals ,Humans ,Transcription factor ,residual tumor ,biology ,business.industry ,Liver Neoplasms ,General Medicine ,NR2F6 ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,Cancer research ,Catheter Ablation ,Disease Progression ,Female ,business ,Biological regulation ,TP248.13-248.65 ,Biotechnology ,Research Article ,Research Paper ,overexpression - Abstract
Hepatoblastoma is a kind of extreme malignancy frequently diagnosed in children. Although surgical resection is considered as the first-line treatment for hepatoblastoma, a relatively large population of patients have lost the preferred opportunity for surgery. Administration of locoregional ablation enables local tumor control but with the deficiency of insufficient ablation, residual tumor, and rapid progression. In this study, we integrated 219 hepatoblastoma and 121 non-cancer liver tissues to evaluate the expression of NR2F6, from which a higher NR2F6 level was found in hepatoblastoma compared with non-cancer livers with a standard mean difference (SMD) of 1.04 (95% CI: 0.79, 1.29). The overexpression of NR2F6 also appeared to be an efficient indicator in distinguishing hepatoblastoma tissues from non-cancer liver tissues from the indication of a summarized AUC of 0.90, with a pooled sensitivity of 0.76 and a pooled specificity of 0.89. Interestingly, nude mouse xenografts provided direct evidence that overexpressed NR2F6 was also detected in residual tumor compared to untreated hepatoblastoma. Chromatin immunoprecipitation-binding data in HepG2 cells and transcriptome analysis of HepG2 xenografts were combined to identify target genes regulated by NR2F6. We finally selected 150 novel target genes of NR2F6 in residual tumor of incomplete ablation, and these genes appeared to be associated with the biological regulation of lipid metabolism-related pathway. Accordingly, targeting NR2F6 holds a therapeutic promise in treating residual recurrent hepatoblastoma after incomplete ablation., GRAPHICAL ABSTRACT
- Published
- 2021