Abstract
BackgroundThe 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.MethodsUsing 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).ResultsExpression 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.ConclusionsIn 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.
Highlights
The clinical significance of microRNAs in intrahepatic cholangiocarcinoma (ICC) is unclear
There have only been three studies on miRNA expression profiles in ICC tissue samples: the first identified a 38-miRNA signature in 27 ICC tissues for distinguishing ICC from normal tissue [18], the second established a 23-miRNA signature associated with tumor subtypes and prognosis in 23 ICCs and combined hepatocellular-cholangiocarcinomas [19], and the third found that different miRNA profiles correlated with the histological grade and the subtype of 15 ICCs induced by liver fluke Opisthorchis viverrini [20]
Our data showed that 158 miRNAs (77 up-regulated miRNAs and 81 downregulated) were differentially expressed in tumor tissues compared with normal intrahepatic bile ducts (NIBD), and a 30-miRNA signature was established for discriminating ICC from NIBD with 100% accuracy
Summary
The clinical significance of microRNAs (miRNAs) in intrahepatic cholangiocarcinoma (ICC) is unclear. Intrahepatic cholangiocarcinoma (ICC) is a high-grade malignant neoplasm originating from the small bile duct epithelium in the liver [1], and is the second most common intrahepatic primary tumor after hepatocellular carcinoma (HCC). It comprises 5.4% of primary liver neoplasms [2]. We analyzed the miRNA expression profiles in 63 patients with ICC and nine normal intrahepatic bile ducts (NIBD) using a custom microarray containing probes for 1,094 miRNAs. The aim of the present study was to identify miRNA signatures that could be used as a biomarker for prognosis in patients with ICC and provided insight for further investigation into the mechanisms involved in ICC development and progression
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