Characterization of hepatocellular adenoma and carcinoma using microRNA profiling and targeted gene sequencing
Autor: | Eran Sadot, T. Peter Kingham, Michael I. D’Angelica, Peter J. Allen, Andrea Ventura, Ronald P. DeMatteo, David S. Klimstra, Jian Zheng, William R. Jarnagin, Joana A. Vigidal, Vinod P. Balachandran |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Viral Diseases Cirrhosis Molecular biology DNA Mutational Analysis lcsh:Medicine Pilot Projects Pathology and Laboratory Medicine Biochemistry Hepatitis Sequencing techniques Medicine and Health Sciences Cluster Analysis lcsh:Science Immune Response beta Catenin Aged 80 and over Multidisciplinary Liver Diseases Liver Neoplasms RNA sequencing Genomics Middle Aged Adenomas Immunohistochemistry 3. Good health Nucleic acids Gene Expression Regulation Neoplastic Infectious Diseases Oncology Hepatocellular carcinoma Female Research Article Adult Carcinoma Hepatocellular Adenoma Immunology Gastroenterology and Hepatology Carcinomas Adenoma Liver Cell 03 medical and health sciences Signs and Symptoms Diagnostic Medicine microRNA Gastrointestinal Tumors medicine Carcinoma Genetics Biomarkers Tumor Humans Non-coding RNA Aged Inflammation Sequence Assembly Tools Biology and life sciences business.industry Sequence Analysis RNA lcsh:R Cancers and Neoplasms Computational Biology Hepatocellular Carcinoma Sequence Analysis DNA Hepatocellular adenoma medicine.disease Genome Analysis digestive system diseases Gene regulation Research and analysis methods MicroRNAs 030104 developmental biology Molecular biology techniques Cancer research RNA lcsh:Q Gene expression business |
Zdroj: | PLoS ONE, Vol 13, Iss 7, p e0200776 (2018) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Background Hepatocellular adenomas (HCA) are benign liver tumors that may transform into hepatocellular carcinoma (HCC), but the molecular drivers of this transformation remain ill-defined. This study evaluates the molecular changes in HCA and HCC and in comparison to their adjacent non-neoplastic liver. Methods 11 patients with HCA and 10 patients with HCC without underlying hepatitis or cirrhosis were included in this pilot study. Tumor and non-tumor liver tissues were selected for immunohistochemical staining, small RNA sequencing, and targeted gene sequencing. We compared microRNA expressions and mutations between HCA and HCC and non-neoplastic liver. Results HCA were classified as inflammatory (n = 6), steatotic (n = 4), or β-catenin activated (n = 1) subtypes. MicroRNA profile of all 3 HCA subtypes clustered between that of normal liver and HCC in principal component analysis. In both HCA and HCC, miR-200a, miR-429, and miR-490-3p were significantly downregulated compared to normal liver, whereas miR-452, miR-766, and miR-1180 were significantly upregulated. In addition, compared to HCA, HCC had significantly higher expression of members of the chromosome 19 miRNA cluster (C19MC), including miR-515-5p, miR-517a, miR-518b, and miR-520c-3p. Conclusions This study indicates that while there are significant differences in the molecular profile between HCA and HCC, several miRNAs are similarly deregulated in HCA and HCC compared to adjacent normal liver. These results may provide insights into the drivers of hepatocarcinogenesis and warrant further investigations. |
Databáze: | OpenAIRE |
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