Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis

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• 作者：Mei-Yin Zhang (1) (2)
  Shu-Hong Li (1) (2) (3)
  Guo-Liang Huang (4)
  Guo-He Lin (1) (2)
  Ze-Yu Shuang (1) (2) (3)
  Xiang-Ming Lao (1) (2) (3)
  Li Xu (1) (2) (3)
  Xiao-Jun Lin (1) (2) (3)
  Hui-Yun Wang (1) (2)
  Sheng-Ping Li (1) (2) (3)
  
  1. State Key Laboratory of Oncology in South China ; Sun Yat-Sen University Cancer Center ; Guangzhou ; 510060 ; China
  2. National Collaborative Innovation Center for Cancer Medicine ; Sun Yat-Sen University Cancer Center ; Guangzhou ; 510060 ; China
  3. Department of Hepatobiliary Oncology ; Sun Yat-Sen University Cancer Center ; Guangzhou ; 510060 ; China
  4. Sino-American Cancer Research Institute ; Guangdong Medical College ; Dongguan ; 523808 ; China
  
• 关键词：microRNA ; Intrahepatic cholangiocarcinoma ; Biomarker ; Prognosis
• 刊名：BMC Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：865 KB
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• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

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.