Murakami Yoshiki, Kubo Shoji, Tamori Akihiro, Itami Saori, Kawamura Etsushi, Iwaisako Keiko, Ikeda Kazuo, Kawada Norifumi, Ochiya Takahiro, Taguchi Y-h
Department of Hepatology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Sci Rep. 2015 Nov 5;5:16294. doi: 10.1038/srep16294.
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.
肝内胆管癌（ICC）和肝细胞癌（HCC）是起源于肝脏的恶性肿瘤。在这两种癌症中，ICC的预后更差，因为它没有可靠的诊断标志物，其致癌机制也尚未完全明确。本研究的目的是整合代谢组学和转录组学数据集，以确定ICC和HCC致癌机制中是否存在差异。研究纳入了10例接受手术切除的ICC患者和6例接受手术切除的HCC患者。通过微阵列对ICC和HCC及其相应的非肿瘤组织（ICC_NT和HCC_NT）进行miRNA和mRNA表达分析。使用毛细管电泳飞行时间质谱（CE-TOFMS）进行化合物分析。主成分分析（PCA）显示，在四个样本组（ICC、ICC_NT、HCC和HCC_NT）中，有14种化合物、62种mRNA和17种miRNA呈现出两种不同的模式：肿瘤和非肿瘤，以及ICC和非ICC。我们通过其化合物的独特模式准确地（84.38%）区分了ICC。使用转录组和代谢组进行的通路分析表明，肿瘤和非肿瘤样本之间有几种通路存在差异。基于PCA的结果，我们认为ICC和HCC具有不同的致癌机制，因此了解基因和化合物的特定特征可能有助于ICC的诊断。
