title: Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis.
abstract: BACKGROUND
  The clinical significance of microRNAs (miRNAs) in intrahepatic cholangiocarcinoma (ICC) is unclear. The objective of this study is to examine the miRNA expression profiles and identify a miRNA signature for the prognosis of ICC.
  
  
  METHODS
  Using a custom microarray containing 1,094 probes, the miRNA expression profiles of 63 human ICCs and nine normal intrahepatic bile ducts (NIBD) were assessed. The miRNA signatures were established and their clinical significances in ICC were analyzed. The expression levels of some miRNAs were verified by quantitative real-time RT-PCR (qRT-PCR).
  
  
  RESULTS
  Expression profile analysis showed 158 differentially expressed miRNAs between ICC and NIBD, with 77 up-regulated and 81 down-regulated miRNAs. From the 158 differentially expressed miRNAs, a 30-miRNA signature consisting of 10 up-regulated and 20 down-regulated miRNAs in ICC was established for distinguishing ICC from NIBD with 100% accuracy. A separate 3-miRNA signature was identified for predicting prognosis in ICC. Based on the 3-miRNA signature, a formula was constructed to compute a risk score for each patient. The patients with high-risk had significantly lower overall survival and disease-free survival than those with low-risk. The expression level of these three miRNAs detected by microarray was verified by qRT-PCR. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic predictor.
  
  
  CONCLUSIONS
  In this study, a 30-miRNA signature for distinguishing ICC from NIBD, and a 3-miRNA signature for evaluating prognosis of ICC were established, which might be able to serve as biomarkers for prognosis of ICC. Further studies focusing on these miRNAs may shed light on the mechanisms associated with ICC pathogenesis and progression.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangmy@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. zhangmy@sysucc.org.cn.
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishh@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishh@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishh@sysucc.org.cn.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Li
authors.affiliation: Sino-American Cancer Research Institute, Guangdong Medical College, Dongguan, 523808, China. huang.glen@gmail.com.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lingh@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lingh@sysucc.org.cn.
authors.forename: Guo-He
authors.initials: GH
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. shuangzy@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. shuangzy@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. shuangzy@sysucc.org.cn.
authors.forename: Ze-Yu
authors.initials: ZY
authors.lastname: Shuang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. laoxm@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. laoxm@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. laoxm@sysucc.org.cn.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Lao
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. xuli@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. xuli@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. xuli@sysucc.org.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. linxj@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. linxj@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. linxj@sysucc.org.cn.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. wanghyun@mail.sysu.edu.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. wanghyun@mail.sysu.edu.cn.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishp@sysucc.org.cn.|National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishp@sysucc.org.cn.|Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. lishp@sysucc.org.cn.
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D059467:Transcriptome; D055815:Young Adult
chemical_list: D035683:MicroRNAs