title: Identification of recurrence-related microRNAs in hepatocellular carcinoma following liver transplantation.
abstract: Tumor recurrence-related microRNAs (miRNAs) in hepatocellular carcinoma (HCC) following orthotopic liver transplantation (OLT) are not clear yet. This study was designed to determine whether altered miRNA expression is associated with HCC recurrence and prognosis following OLT. 18 miRNAs, including 6 up-regulated and 12 down-regulated miRNAs were identified by microarray in primary HCC samples of patients who had developed HCC recurrence (n = 5) compared to those with non-recurrence (n = 5) following OLT by using p < 0.05 as cutoff value. The six most significantly altered miRNAs (fold change ≥ 2: miR-19a, miR-886-5p, miR-126, miR-223, miR-24 and miR-147) were further confirmed by qRT-PCR in the remaining 105 HCC samples. In receiver-operating characteristic curve analysis, this six miRNAs were of high sensitivity and specificity in predicting HCC recurrence. Using Cox regression and risk score analysis, we built a six-miRNA signature based on their qRT-PCR readings for the prediction of outcome of HCC following OLT. Kaplan-Meier and Cox proportional regression revealed this six-miRNA signature was a significant independent predictor of overall survival (log-rank p = 0.020) and recurrence-free survival (log-rank p < 0.001). Finally, the data were further reconfirmed in an independent cohort of 50 patients from another transplant center. In addition, bioinformatics Gene Ontology and pathway analysis were also performed to better understand the critical roles of these miRNAs in HCC recurrence. Our study, in addition to suggesting a different miRNA expression pattern between HCC samples of patients with recurrence and those with non-recurrence, proposes that this six-miRNA signature may serve as biomarker for prognosis of HCC patients following OLT.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Zhong-Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.forename: Mu-Jian
authors.initials: MJ
authors.lastname: Teng
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Fan
authors.forename: Hua-Mei
authors.initials: HM
authors.lastname: Tang
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Wu
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
authors.forename: Zhao-Wen
authors.initials: ZW
authors.lastname: Wang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Qiu
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Peng
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs