title: Expression of serum miR-218 in hepatocellular carcinoma and its prognostic significance.
abstract: BACKGROUND
  Several recent studies have revealed that microRNAs (miRNAs) are stably detectable in the circulation and can be used as biomarkers for diagnosis and prognosis of malignancy. The aim of this manuscript is to investigate serum miR-218 expression in patients with hepatocellular carcinoma (HCC) and to analyze its potential diagnostic and prognostic value in HCC.
  
  
  METHODS
  Quantitative real-time quantitative PCR (qPCR) was conducted to detect serum miR-218 expression from 156 HCC and 98 benign liver diseases (BLD) as well as 64 healthy controls. The relevance of serum miR-218 expression to the clinicopathological factors was assessed. In addition, the prediction of cutoff values of the markers was performed by the receiver operating characteristic (ROC) curve. Moreover, the Kaplan-Meier method was used to plot survival curves and univariable and multivariable Cox regression analyses were used to evaluate independent prognostic factors.
  
  
  RESULTS
  Consequently, our findings revealed that serum miR-218 levels were remarkably underexpressed in HCC patients as compared to BLD patients and healthy controls. And its low level was obviously related to tumor size (p = 0.048), tumor number (p = 0.018), vascular invasion (p = 0.039), Edmondson grade (p = 0.042), and higher TNM stage (III-IV). ROC curve analysis showed that miR-218 had a significant diagnostic accuracy, yielded an AUC (the areas under the ROC curve) of 0.734 (95 % confidence interval (CI) 0.68-0.789, p < 0.01), thus providing a sensitivity of 66.7 % and a specificity of 69.1 % in discriminating HCC from BLD and healthy controls. Meanwhile, miR-218 can act as a useful biomarker in distinguishing the patients with large tumors (>5 cm) from patients with small tumors (<5 cm) (p < 0.01). In addition, the combination of miR-218 and AFP had greater diagnosis capacity with an AUC of 0.908 (95 % CI 0.876-0.940; p < 0.01). Both log-rank test and Cox regression analysis demonstrated that the decreased serum expression of miR-218 had a significant impact on overall survival of the patients with HCC (HR = 3.049, 95 % CI 2.028-4.585, p < 0.01).
  
  
  CONCLUSIONS
  Taken together, this study suggested that serum expression of miR-218 might be a potential noninvasive tumor biomarker in the diagnosis and assessment of prognosis of HCC.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Ningbo First Hospital, Ningbo, 315010, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Ningbo First Hospital, Ningbo, 315010, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Ningbo First Hospital, Ningbo, 315010, China.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Ningbo First Hospital, Ningbo, 315010, China.
authors.forename: G
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Ningbo First Hospital, Ningbo, 315010, China. jiansjdoctor@yeah.net.
authors.forename: J
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C547471:MIRN218 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Diagnostic marker; Hepatocellular carcinoma; Prognostic marker; miR-218