Cytokines and hepatocellular carcinoma: Potential progression markers and cell typespecific modulators of the mirnome (Interleukin-6 and JAK/STAT activating cytokines)
Cytokines and hepatocellular carcinoma: Potential progression markers and cell typespecific modulators of the mirnome (Interleukin-6 and JAK/STAT activating cytokines)
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细胞因子和肝细胞癌：微小组的潜在进展标记物和细胞类型特异性调节剂（Interleukin-6 和 JAK/STAT 激活细胞因子）
DOI：
10.1055/s-0036-1597466
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
I. Behrmann
中科院分区：
文献类型：
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作者：
Kirchmeyer;F. A. Servais;M. Hamdorf;C. Haan;P. Nazarov;L. Vallar;M. Casper;M. Glanemann;A. Arslanow;C. Rubie;F. Lammert;S. Kreis;I. Behrmann
研究方法：到目前为止，已经用Luminex免疫测定技术（Bio-Rad 2200，Bio-Rad）分析了8名健康对照、23名非酒精性脂肪性肝炎（NASH）患者和18名HCC患者的血清样品中多达48种细胞因子的水平。四种细胞因子的作用：Hyper-IL-6（H-IL-6）、OSM、IFN-γ和IL-27对来自人肝、结肠和皮肤细胞的9种健康和癌细胞系的miRNome和转录组的影响（PH5CH8，Hep3B，Huh-7; NCM460，HCT 15，HCT 116; NHEM，A375，MelJuso）已经通过微阵列分析（Affyssin GeneChip miRNA Array 3.0，Human Transcriptome Array 2.0）并通过qPCR验证。在第一步中，我们分析并关联了HCC和NASH患者中炎性细胞因子的表达水平，这些患者处于发展HCC的高风险中。在此，通过Bio-ELISA细胞因子免疫测定证实，HCC患者的血清IL-6和HGF水平高于健康对照和晚期NASH患者。接下来，我们想研究NASH患者中细胞因子水平与PNPLA 3 p.148 M风险变体存在之间的可能相关性，从而有助于肝病生物标志物研究。
Methods: So far, serum samples of 8 healthy controls, 23 nonalcoholic steatohepatitis (NASH) patients and 18 HCC patients have been analyzed regarding the levels of up to 48 cytokines with the Luminex immunoassay technology (Bio-Plex 2200, Bio-Rad). The effect of four cytokines: Hyper-IL-6 (H-IL-6), OSM, IFN-γ, and IL-27 on the miRNome and on the transcriptome of nine healthy and cancerous cell lines derived from human liver, colon and skin cells (PH5CH8, Hep3B, Huh-7; NCM460, HCT15, HCT116; NHEM, A375, MelJuso) has been analyzed by microarray (Affymetrix GeneChip miRNA Array 3.0, Human Transcriptome Array 2.0) and validated by qPCR.Results: In a first step, we analyzed and correlated the expression levels of inflammatory cytokines in HCC and NASH patients, being at high risk to develop HCC. Herein, serum levels of IL-6 and of HGF were higher in HCC patients than in healthy controls and in advanced NASH patients, as confirmed by Bio-Plex cytokine immunoassays. Next, we wanted to study a possible correlation between cytokine levels and the presence of the PNPLA3 p. 148 M risk variant in patients with NASH, thereby contributing to biomarker research in liver diseases.