title: Early-phase circulating miRNAs predict tumor recurrence and survival of hepatocellular carcinoma patients after liver transplantation.
abstract: Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Kevin Tak-Pan
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Chung Mau
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Chang Xian
authors.initials: CX
authors.lastname: Li
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Geng
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Oscar Wai-Ho
authors.initials: OW
authors.lastname: Yeung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Yuen Yuen
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.
authors.forename: See Ching
authors.initials: SC
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000601:surgery; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C577700:MIRN1246 microRNA, human; D035683:MicroRNAs
keywords: HCC recurrence; early-phase; liver transplantation; macrophage activation; miR-1246