Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are liver originated malignant tumors. Of the two, ICC has the worse prognosis because it has no reliable diagnostic markers and its carcinogenic mechanism is not fully understood. The aim of this study was to integrate metabolomics and transcriptomics datasets to identify variances if any in the carcinogenic mechanism of ICC and HCC. Ten ICC and 6 HCC who were resected surgically, were enrolled. miRNA and mRNA expression analysis were performed by microarray on ICC and HCC and their corresponding non-tumor tissues (ICC_NT and HCC_NT). Compound analysis was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Principle component analysis (PCA) revealed that among the four sample groups (ICC, ICC_NT, HCC, and HCC_NT) there were 14 compounds, 62 mRNAs and 17 miRNAs with two distinct patterns: tumor and non-tumor, and ICC and non-ICC. We accurately (84.38%) distinguished ICC by the distinct pattern of its compounds. Pathway analysis using transcriptome and metabolome showed that several pathways varied between tumor and non-tumor samples. Based on the results of the PCA, we believe that ICC and HCC have different carcinogenic mechanism therefore knowing the specific profile of genes and compounds can be useful in diagnosing ICC.

BackgroundMany studies support the hypothesis that specific microRNA (miRNA) expression in various human cancers including hepatocarcinogenesis is closely associated with diagnosis and prognosis. In hepatocellular carcinoma (HCC), malignancy level is related to the degree of histological differentiation.MethodsIn order to establish a novel biomarker that can determine the degree of malignancy and forecast patient prognosis, we performed a microarray analysis to investigate the miRNA expression profiles in 110 HCC which were comprised of 60 moderately, 30 poorly, and 20 well differentiated HCC.ResultsWe found that the expression of 12 miRNAs varied significantly according to the degree of histological differentiation. Particularly, miR-18b expression in poorly differentiated HCC was significantly higher than in well differentiated HCC. Based on miRanda and Targetscan target search algorithms and Argonaute 2 immunoprecipitation study, we noted that miR-18b can control the expression of trinucleotide repeat containing 6B (TNRC6B) as a target gene. Additionally, in two hepatoma cell lines, we found that over-expression of miR-18b or down-regulation of TNRC6B accelerated cell proliferation and loss of cell adhesion ability. Finally, we observed that after surgical resection, HCC patients with high miR-18b expression had a significantly shorter relapse-free period than those with low expression.ConclusionsmiR-18b expression is an important marker of cell proliferation and cell adhesion, and is predictive of clinical outcome. From a clinical point of view, our study emphasizes miR-18b as a diagnostic and prognostic marker for HCC progression.

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Previously, we have reported that 1- and 3-isoTQENs (N,N,N',N'-tetrakis(1- or 3-isoquinolylmethyl)ethylenediamines) exhibit a specific fluorescence enhancement toward zinc ion. In this study, three methoxy-substituted derivatives of 1-isoTQEN were synthesized and their fluorescent response toward zinc ion was studied. The substitution pattern of the methoxy group significantly changes the solubility of compounds in aqueous DMF, λ(max) in the absorption spectra, excitation/emission wavelengths and fluorescence intensity of zinc complexes. In the presence of zinc ion, 7-MeO-1-isoTQEN exhibits higher fluorescence intensity and longer excitation/emission wavelengths (λ(ex) = 342 nm, λ(em) = 526 nm) than 6-MeO-1-isoTQEN (λ(ex) = 303 nm, λ(em) = 469 nm) and 5,6,7-triMeO-1-isoTQEN (λ(ex) = 340 nm, λ(em) = 504 nm). The fluorescence intensity of a zinc complex of 7-MeO-1-isoTQEN (ϕ = 0.122) is four times higher than the parent 1-isoTQEN (ϕ = 0.034) under the same conditions. The crystal structure of 7-MeO-1-isoTQEN-Zn complex reveals that all six nitrogen atoms participate to the metal coordination with ideal octahedral geometry, affording significantly high metal binding affinity comparable with TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine). 7-MeO-1-isoTQEN detects zinc ion concentration change in cells by fluorescence microscopic analysis.

Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced mouse model of AD.