title: Diagnostic value of miRNA-96-5p/3p in dysplastic nodules and well-differentiated small hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocarcinogenesis is a multistep process from cirrhosis through low-grade dysplastic nodule, high-grade dysplastic nodule to hepatocellular carcinoma. Differential diagnosis between high-grade dysplastic nodules and early hepatocellular carcinomas is particularly difficult. The present study aims to identify a novel biological marker for differential diagnosis of the two lesions.
  
  
  METHODS
  The expression level of an miRNA pair, miRNA-96-5p and 3p, was assessed by reverse transcription polymerase chain reaction in hepatic tissues.
  
  
  RESULTS
  We showed that mature miRNA-96-5p and passenger strand miRNA-96-3p were differentially expressed in multistep hepatocarcinogenesis. miRNA-96-5p was significantly upregulated from cirrhosis, dysplastic nodules to hepatocellular carcinoma. However, significance of determination of miRNA-96-5p expression level for differential diagnosis between high-grade dysplastic nodule and hepatocellular carcinoma is limited. In contrast, the expression of miRNA-96-3p was detectable in cirrhosis and dysplastic nodules. Also, it was completely undetectable in the majority of hepatocellular carcinomas (30/34, 88.2%). The sensitivity and specificity of miRNA-96-3p negative expression for differential diagnosis of hepatocellular carcinomas from high-grade dysplastic nodules were 88.2% and 84.2%, respectively. In addition, a more specific diagnosis could be carried out by combining miRNA-96-3p with glypican 3, with the specificity of 100%.
  
  
  CONCLUSIONS
  These findings demonstrated that miRNA-96-3p is a helpful diagnostic biomarker in differential diagnosis between high-grade dysplastic nodules and well-differentiated small hepatocellular carcinomas, especially in combination with glypican 3.
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Ai-Yan
authors.initials: AY
authors.lastname: Xing
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Ran-Ran
authors.initials: RR
authors.lastname: Ma
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Shandong Cancer Hospital and Institute, Jinan, P.R. China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
keywords: differential diagnosis; dysplastic nodule; hepatocarcinogenesis; miRNA-96-3p; miRNA-96-5p