title: Serum miR-224 as a biomarker for detection of hepatocellular carcinoma at early stage.
abstract: OBJECTIVE
  Circulating microRNAs (miRNAs) are known as potential noninvasive biomarkers for cancers. Overexpression of mircoRNA-224 (miR-224) has been reported in hepatocellular carcinoma (HCC), so the aim of this study was to determine the value of serum miR-224 in diagnosis of HCC at early stage.
  
  
  METHODS
  Three hundred and thirty-five subjects including early-stage HCC, liver cirrhosis (LC), chronic hepatitis B (CHB) and healthy controls (HC) were enrolled in two cohorts. Association of miR-224 expression with HCC was analyzed. The area under curves (AUC) was calculated for miR-224 and compared with that for AFP in detection of HCC at early stage.
  
  
  RESULTS
  Our results demonstrated that serum miR-224 was significantly higher in early-stage HCC than that in LC, CHB and HC, respectively. Besides, it decreased significantly after surgery in early-stage HCC, and there was a positive correlation between miR-224 in sera and that in paired tumor tissues. Serum miR-224 levels also showed a significant correlation with BCLC stages of HCC. Expression of miR-224 was significantly higher in tumorous tissues than that in adjacent non-tumorous tissues of HCC, pathologic liver tissues of LC and CHB. Further, ROC analysis demonstrated that AUC were 0.880 (95% CI: 0.838-0.923; sensitivity: 86.5%, specificity: 76.7%) for serum miR-224 in discriminating early-stage HCC from all three controls (LC, CHB and healthy subjects), higher than that for AFP (AUC: 0.700, 95% CI: 0.633-0.767; sensitivity: 71.9%, specificity: 63.7%) (P<0.01). Moreover, serum miR-224 also had a better performance than AFP in discriminating HCC from each of the three control groups. When miR-224 and AFP were used together, the diagnostic accuracy increased significantly compared with either marker alone.
  
  
  CONCLUSIONS
  These results indicate that serum miR-224 is a potential reliable biomarker in detecting early-stage HCC, with better performance than AFP.
authors.affiliation: Department of General Surgery (Hepatobiliary Surgery), Shaoxing People's Hospital, Shaoxing, PR China; Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of General Surgery (Hepatobiliary Surgery), Shaoxing People's Hospital, Shaoxing, PR China; Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, PR China.
authors.forename: Baochun
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of General Surgery (Hepatobiliary Surgery), Shaoxing People's Hospital, Shaoxing, PR China; Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Linyi People's Hospital, Linyi 276000, Shandong Province, PR China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Emergency, Linyi People's Hospital, No. 27 Jiefang Road, Linyi 276000, Shandong Province, PR China. Electronic address: aijinzhouly@163.com.
authors.forename: Aijin
authors.initials: A
authors.lastname: Zhou
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D000509:alpha-Fetoproteins