論文 - 詳細
| RRC ID | 50461 |
|---|---|
| 著者 | Chiyonobu N, Shimada S, Akiyama Y, Mogushi K, Itoh M, Akahoshi K, Matsumura S, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Suganami T, Yamaoka S, Ogawa Y, Tanabe M, Tanaka S. |
| タイトル | Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors. |
| ジャーナル | Am J Pathol |
| Abstract |
Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC); however, tumor-specific biomarkers still remain unclear. We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout mice, which develop HCC with obesity, insulin resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and melanocortin 4 receptor-knockout mice into two distinct subgroups, one of which included mouse HCC and was causatively associated with metabolic risk factors. Nine genes commonly overexpressed in human and mouse metabolic disease-associated HCC were identified; fatty acid binding protein 4 (FABP4) was remarkably enriched in intratumoral activated hepatic stellate cells (HSCs). Subclones constitutively expressing FABP4 were established from a human HSC cell line in which expression levels of inflammatory chemokines, including IL-1A and IL-6, were up-regulated through NF-κB nuclear translocation, resulting in recruitment of macrophages. An immunohistochemical validation study of 106 additional human HCC samples indicated that FABP4-positive HSCs were distributed in tumors of 38 cases, and the FABP4-high group consisted of patients with nonviral and nonalcoholic HCC (P = 0.027) and with multiple metabolic risk factors (P < 0.001) compared with the FABP4-low group. Thus, FABP4 overexpression in HSCs may contribute to hepatocarcinogenesis in patients with metabolic risk factors by modulation of inflammatory pathways. |
| 巻・号 | 188(5) |
| ページ | 1213-1224 |
| 公開日 | 2018-5-1 |
| DOI | 10.1016/j.ajpath.2018.01.012 |
| PII | S0002-9440(17)30959-8 |
| PMID | 29454748 |
| MeSH | Animals Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Proliferation Fatty Acid-Binding Proteins / genetics Fatty Acid-Binding Proteins / metabolism* Hepatic Stellate Cells / metabolism* Hepatic Stellate Cells / pathology Humans Interleukin-1alpha / genetics Interleukin-1alpha / metabolism Interleukin-6 / genetics Interleukin-6 / metabolism Liver / metabolism Liver / pathology Liver Neoplasms / genetics Liver Neoplasms / metabolism* Liver Neoplasms / pathology Mice Mice, Knockout Receptor, Melanocortin, Type 4 / genetics Receptor, Melanocortin, Type 4 / metabolism Risk Factors |
| IF | 3.491 |
| 引用数 | 8 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-EF-MCS (RDB04378). |