論文 - 詳細
| RRC ID | 36933 |
|---|---|
| 著者 | Xu YF, Ge FJ, Han B, Yang XQ, Su H, Zhao AC, Zhao MH, Yang YB, Yang J. |
| タイトル | High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma. |
| ジャーナル | World J Gastroenterol |
| Abstract |
AIM:To evaluate the prognostic value of high-mobility group box 1 (HMGB1) expression in intrahepatic cholangiocarcinoma (IHCC) and the possible underlying mechanism. METHODS:Tissue microarray was constructed from 65 IHCC patients. Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C (VEGF-C). Real-time PCR and Western blot analyses were used to study transcript and protein levels. The interaction between HMGB1 and VEGF-C was evaluated by siRNA, real-time PCR, and enzyme-linked immuno assays. The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed by χ (2) test, and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Cox-regression model, respectively. RESULTS:Overall, overexpression of HMGB1 was found in 38/65 (58.8%) IHCCs, whereas VEGF-C overexpression was present in 30/65 (46.2%) cases. Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density (P = 0.031, r = 0.268) and VEGF-C expression (P = 0.041, r = 0.254). With univariate analysis, both HMGB1 (P = 0.001) and VEGF-C (P = 0.004) were identified to be significantly associated with overall survival rate. Multivariate analysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs (P = 0.005). siRNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) by elevating E-Cadherin expression and reducing expression of N-Cadherin, Vimentin and Snail in RBE cells. Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C, whereas the recombinant HMGB1 increased the VEGF-C level in RBE cells (both P < 0.05), which suggested that HMGB1 could promote lymphatic microvessel density, and subsequently lymphatic invasion, via promoting VEGF-C expression. CONCLUSION:Our results define an important role of HMGB1 in the progression of cholangiocarcinoma, and HMGB1 may serve as a prognostic marker for IHCC patients. |
| 巻・号 | 21(11) |
| ページ | 3256-65 |
| 公開日 | 2015-3-21 |
| DOI | 10.3748/wjg.v21.i11.3256 |
| PMID | 25805932 |
| PMC | PMC4363755 |
| MeSH | Adult Aged Aged, 80 and over Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism* Bile Duct Neoplasms / mortality Bile Duct Neoplasms / pathology* Bile Ducts, Intrahepatic / metabolism* Bile Ducts, Intrahepatic / pathology* Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Line, Tumor Chi-Square Distribution Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism* Cholangiocarcinoma / mortality Cholangiocarcinoma / secondary* Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic HMGB1 Protein / genetics HMGB1 Protein / metabolism* Humans Kaplan-Meier Estimate Lymphangiogenesis Lymphatic Metastasis Lymphatic Vessels / metabolism Lymphatic Vessels / pathology Male Middle Aged Multivariate Analysis Prognosis Proportional Hazards Models RNA Interference RNA, Messenger / metabolism Risk Factors Time Factors Transfection Vascular Endothelial Growth Factor C / metabolism |
| IF | 3.665 |
| 引用数 | 36 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HuCCT1(RCB1960) |