BACKGROUND: It is known that malignant transformation to hepatocellular carcinoma (HCC) occurs at a higher frequency in hepatocellular adenoma (HCA) from type I glycogen storage disease (GSD I) compared to HCA from other etiologies. In this study, we aimed to identify differentially expressed miRNAs in GSD Ia HCA as candidates that could serve as putative biomarkers for detection of GSD Ia HCA and/or risk assessment of malignant transformation. METHODS: Utilizing massively parallel sequencing, the miRNA profiling was performed for paired adenomas and normal liver tissues from seven GSD Ia patients. Differentially expressed miRNAs were validated in liver tumor tissues, HCC cell lines and serum using quantitative RT-PCR. RESULTS: miR-34a, miR-34a, miR-224, miR-224, miR-424, miR-452 and miR-455-5p were found to be commonly deregulated in GSD Ia HCA, general population HCA, and HCC cell lines at compatible levels. In comparison with GSD Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b-5p, and miR-214 were more significant in HCC cell lines. Furthermore, serum level of miR-130b in GSD Ia patients with HCA was moderately higher than that in either GSD Ia patients without HCA or healthy individuals. CONCLUSION: We make the first observation of distinct miRNA deregulation in HCA associated with GSD Ia. We also provide evidence that miR-130b could serve as a circulating biomarker for detection of GSD Ia HCA. This work provides prominent candidate miRNAs worth evaluating as biomarkers for monitoring the development and progress of liver tumors in GSD Ia patients in the future.
BACKGROUND: It is known that malignant transformation to hepatocellular carcinoma (HCC) occurs at a higher frequency in hepatocellular adenoma (HCA) from type I glycogen storage disease (GSD I) compared to HCA from other etiologies. In this study, we aimed to identify differentially expressed miRNAs in GSD Ia HCA as candidates that could serve as putative biomarkers for detection of GSD Ia HCA and/or risk assessment of malignant transformation. METHODS: Utilizing massively parallel sequencing, the miRNA profiling was performed for paired adenomas and normal liver tissues from seven GSD Iapatients. Differentially expressed miRNAs were validated in liver tumor tissues, HCC cell lines and serum using quantitative RT-PCR. RESULTS:miR-34a, miR-34a, miR-224, miR-224, miR-424, miR-452 and miR-455-5p were found to be commonly deregulated in GSD Ia HCA, general population HCA, and HCC cell lines at compatible levels. In comparison with GSD Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b-5p, and miR-214 were more significant in HCC cell lines. Furthermore, serum level of miR-130b in GSD Iapatients with HCA was moderately higher than that in either GSD Iapatients without HCA or healthy individuals. CONCLUSION: We make the first observation of distinct miRNA deregulation in HCA associated with GSD Ia. We also provide evidence that miR-130b could serve as a circulating biomarker for detection of GSD Ia HCA. This work provides prominent candidate miRNAs worth evaluating as biomarkers for monitoring the development and progress of liver tumors in GSD Iapatients in the future.
Authors: G M Talente; R A Coleman; C Alter; L Baker; B I Brown; R A Cannon; Y T Chen; J F Crigler; P Ferreira; J C Haworth; G E Herman; R M Issenman; J P Keating; R Linde; T F Roe; B Senior; J I Wolfsdorf Journal: Ann Intern Med Date: 1994-02-01 Impact factor: 25.391
Authors: Julien Calderaro; Philippe Labrune; Guillaume Morcrette; Sandra Rebouissou; Dominique Franco; Sophie Prévot; Alberto Quaglia; Pierre Bedossa; Louis Libbrecht; Luigi Terracciano; G Peter A Smit; Paulette Bioulac-Sage; Jessica Zucman-Rossi Journal: J Hepatol Date: 2012-10-06 Impact factor: 25.083
Authors: Erin Connolly; Margherita Melegari; Pablo Landgraf; Tatyana Tchaikovskaya; Bud C Tennant; Betty L Slagle; Leslie E Rogler; Mihaela Zavolan; Thomas Tuschl; Charles E Rogler Journal: Am J Pathol Date: 2008-08-07 Impact factor: 4.307
Authors: Jinmai Jiang; Yuriy Gusev; Ileana Aderca; Teresa A Mettler; David M Nagorney; Daniel J Brackett; Lewis R Roberts; Thomas D Schmittgen Journal: Clin Cancer Res Date: 2008-01-15 Impact factor: 12.531