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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.

Background and Objective: There are few studies about origins of regulatory T (Treg) cells increased in primary hepatocellular carcinoma (HCC) tissue. Studies showed that Treg cells could be induced by transforming growth factor-beta1 (TGF-beta1), but the relation between TGF-beta1 expression and Treg cell infiltration is unclear in HCC tissue. This study was to investigate the expression of TGF-beta1 and correlations with the amount of Treg cells in HCC, and to evaluate their clinical values in predicting the prognosis of HCC., Methods: Envision immunohistochemistry was used to detect the expression of TGF-beta1 and Foxp3 in 102 specimens of HCC tissue and paired adjacent non-tumor liver tissue., Results: Of the 102 specimens of HCC, 41 showed low TGF-beta1 expression and 61 (59.8%) showed high expression; of the 102 specimens of adjacent non-tumor tissue, 22 showed low TGF-beta1 expression and 80 (78.4%) showed high expression. The high expression rate of TGF-beta1 was significantly lower in HCC than in adjacent non-tumor tissues (P = 0.001). Average Foxp3+ cell density in HCC was 2.98 cells/HP, but there was very few or no expression of Foxp3 in adjacent non-tumor liver tissue. Expression of TGF-beta1 was positively correlated with expression of Foxp3 in HCC tissues (r = 0.228, P = 0.021). The expression of TGF-beta1 was significantly higher in HCC tissues with high preoperative AFP concentration than in those with low preoperative AFP concentration (P = 0.023). TGF-beta1 and Foxp3 expression had no correlations with tumor diameter, tumor capsule, liver cirrhosis, and so on. The 5-year survival rate was not different between HCC tissues with high and low TGF-beta1 expression (P = 0.790); however, it was significantly lower in HCC tissues with high Treg cell infiltration than in those low infiltration (25% vs. 44%, P = 0.007). Cox multivariate analysis showed that the number of Treg cells and tumor capsule were independent prognostic factors (P = 0.021, P = 0.001)., Conclusions: Expression of TGF-beta1 may relate to the infiltration of Treg cells in HCC tissues, but the relation need to be further investigated. The number of Treg cells in HCC tissues could be used as a potential immunological prognostic indicator for HCC patients after resection.