| Experiment ID | EXP00181 |
| Reference | Title: Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepaticcholangiocarcinoma. Author: Oishi N, Kumar MR, Roessler S, Ji J, Forgues M, Budhu A, Zhao X, Andersen JB, Ye QH, Jia HL, Qin LX, Yamashita T, Woo HG, Kim YJ, Kaneko S, Tang ZY,Thorgeirsson SS, Wang XW. Journal: Hepatology. 2012 Nov;56(5):1792-803. doi: 10.1002/hep.25890. Epub 2012 Aug 22. Abstract: Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecularcharacteristics are largely unknown. In this study, we conducted transcriptomicprofiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumorspecimens from Asian patients using Affymetrix messenger RNA (mRNA) andNanoString microRNA microarrays to search for unique gene signatures linked totumor subtypes and patient prognosis. We validated the signatures in anadditional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC casesinto two main subgroups, one of which shared gene expression signatures withpreviously identified hepatocellular carcinoma (HCC) with stem cell geneexpression traits. ICC-specific gene signatures could predict survival in AsianHCC cases and independently in Caucasian ICC cases. Integrative analyses of theICC-specific mRNA and microRNA expression profiles revealed that a commonsignaling pathway linking miR-200c signaling to epithelial-mesenchymal transition(EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR-200c resulted in an induction of EMT, whereas activation ofmiR-200c led to a reduction of EMT including a reduced cell migration andinvasion in ICC cells. We also found that miR-200c and neural cell adhesionmolecule 1 (NCAM1) expression were negatively correlated and their expressionlevels were predictive of survival in ICC samples. NCAM1, a known hepaticstem/progenitor cell marker, was experimentally demonstrated to be a directtarget of miR-200c.CONCLUSION: Our results indicate that ICC and HCC share commonstem-like molecular characteristics and poor prognosis. We suggest that thespecific components of EMT may be exploited as critical biomarkers and clinicallyrelevant therapeutic targets for an aggressive form of stem cell-like ICC. PMID: 22707408 |
| Expressiion Profile | Description: Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [miRNA] Organism: Homo sapiens GEO ID: GSE32957 Platform: GPL14732 Number of samples: 35 |
| Design and Sample | Cancer Type: liver cancer Cancer SubType: combined hepatocellular cholangiocarcinoma Cell Line: N/D Experimental Design: cancer vs normal Case Sample: combined hepatocellular cholangiocarcinoma Control Sample: normal liver Num of Case: 7 Num of Control: 5 Quantification Software: Limma Num of miRNAs: 654 |
| Identification | Num of Up: 13 Num of Down: 7 |