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The construction of intrahepatic cholangiocarcinoma model in zebrafish.

ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor, difficult to diagnose even at an early stage. In this study, we successfully constructed an nras ^61K -induced ICC model in zebrafish. Transcriptome analysis and gene set enrichment analysis (GSEA) of liver samples of the ICC and WT (wild-type) zebrafish revealed that the genes differentially expressed between the two groups were mainly involved in focal adhesion, chemokine signaling and metabolic pathways. Analysis of DNA methylomes revealed that compared with WT samples, methylated genes in ICC samples were enriched in functions associated with cellular, single-organism and metabolic processes. In particular, our result discovered eleven potential biomarker genes of ICC which were conserved between zebrafish and humans. Moreover, three potential biomarker genes were hypomethylated in the tumorigenesis of ICC: ehf, epha4 and itgb6. In summary, our study provides a comprehensive analysis of molecular mechanisms accompanying the progressive nras ^61K -induced ICC. This work indicates that our transgenic zebrafish could be a valuable model, not only for studying liver cancer, but also for exploring new therapeutic targets.

SUBMITTER: Wang J

PROVIDER: S-EPMC5645375 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The construction of intrahepatic cholangiocarcinoma model in zebrafish.

Wang Jing J Leng Xiaoqian X Wang Guiping G Wan Xiaoyang X Cao Hong H

Scientific reports 20171017 1

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor, difficult to diagnose even at an early stage. In this study, we successfully constructed an nras <sup>61K</sup> -induced ICC model in zebrafish. Transcriptome analysis and gene set enrichment analysis (GSEA) of liver samples of the ICC and WT (wild-type) zebrafish revealed that the genes differentially expressed between the two groups were mainly involved in focal adhesion, chemokine signaling and metabolic pathways. Analysis of ...[more]

PMID: 29042681

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Project description:An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions.

Dataset Information

The construction of intrahepatic cholangiocarcinoma model in zebrafish.

Publications

The construction of intrahepatic cholangiocarcinoma model in zebrafish.

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