Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus.
Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age- and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chao-Hung
CH
Hung
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Tsung-Hui
TH
Hu
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Sheng-Nan
SN
Lu
Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Fang-Ying
FY
Kuo
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chien-Hung
CH
Chen
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Jing-Houng
JH
Wang
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chao-Min
CM
Huang
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chuan-Mo
CM
Lee
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chih-Yun
CY
Lin
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yi-Hao
YH
Yen
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yi-Chun
YC
Chiu
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis*; D000509:alpha-Fetoproteins / Q000032:analysis
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D000509:alpha-Fetoproteins
diagnosis; dysplastic nodule; hepatitis B virus; hepatocellular carcinoma; microRNAs