Sakura Akamatsu1, C Nelson Hayes1, Masataka Tsuge2, Daiki Miki1, Rie Akiyama1, Hiromi Abe1, Hidenori Ochi1, Nobuhiko Hiraga1, Michio Imamura1, Shoichi Takahashi3, Hiroshi Aikata4, Tomokazu Kawaoka1, Yoshiiku Kawakami1, Waka Ohishi5, Kazuaki Chayama6. 1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan. 2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan; Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan. 3. Koyo New Town Hospital, Hiroshima, Japan. 4. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan. 5. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan. 6. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Electronic address: chayama@hiroshima-u.ac.jp.
Abstract
OBJECTIVES: Patients infected with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) are at greater risk of cirrhosis and hepatocellular carcinoma. The objective of this study was to identify virus-specific serum microRNA profiles associated with liver function and disease progression. Microarray analysis of serum microRNAs was performed using the Toray 3D array system in 22 healthy subjects, 42 HBV patients, and 30 HCV patients. Selected microRNAs were then validated by qRT-PCR in 186 HBV patients, 107 HCV patients, and 22 healthy subjects. RESULTS: Microarray analysis showed up-regulation of a number of microRNAs in serum of both HBV and HCV patients. In qRT-PCR analysis, miR-122, miR-99a, miR-125b, miR-720, miR-22, and miR-1275 were up-regulated both in HBV patients relative to healthy subjects, and all except miR-1275 were up-regulated in HBeAg-positive patients relative to HBeAg-negative patients. Specific microRNAs were independently associated with different aspects of HBV infection. MiR-122 was independently associated with HBV DNA level, whereas miR-125b was independently associated with levels of HBV DNA, HBsAg, and HBeAg. MiR-22 and miR-1275 were independently associated with serum γ-glutamyl transpeptidase levels. CONCLUSIONS: Serum microRNA levels reflect differences in the etiology and stage of viral hepatitis.
OBJECTIVES:Patients infected with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) are at greater risk of cirrhosis and hepatocellular carcinoma. The objective of this study was to identify virus-specific serum microRNA profiles associated with liver function and disease progression. Microarray analysis of serum microRNAs was performed using the Toray 3D array system in 22 healthy subjects, 42 HBVpatients, and 30 HCVpatients. Selected microRNAs were then validated by qRT-PCR in 186 HBVpatients, 107 HCVpatients, and 22 healthy subjects. RESULTS: Microarray analysis showed up-regulation of a number of microRNAs in serum of both HBV and HCVpatients. In qRT-PCR analysis, miR-122, miR-99a, miR-125b, miR-720, miR-22, and miR-1275 were up-regulated both in HBVpatients relative to healthy subjects, and all except miR-1275 were up-regulated in HBeAg-positive patients relative to HBeAg-negative patients. Specific microRNAs were independently associated with different aspects of HBV infection. MiR-122 was independently associated with HBV DNA level, whereas miR-125b was independently associated with levels of HBV DNA, HBsAg, and HBeAg. MiR-22 and miR-1275 were independently associated with serum γ-glutamyl transpeptidase levels. CONCLUSIONS: Serum microRNA levels reflect differences in the etiology and stage of viral hepatitis.
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