High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy.

High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy.
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DOI:
10.1186/1479-5876-10-135
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发表时间:
2012-07-02
影响因子:
7.4
通讯作者:
Chen M
Chen M
中科院分区:
医学2区
文献类型:
--
作者:
Liu F;Zhang Y;Peng Z;Gao H;Xu L;Chen M

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高迁移率族蛋白1(HMGB 1)过表达已在多种人类癌症中报道。然而,HMGB 1在肝细胞癌(HCC)中的作用仍不清楚。本研究的目的是分析HMGB 1蛋白在肝癌、癌旁和正常组织中的表达,并评估其对肝癌根治性切除术后预后的意义。应用逆转录-聚合酶链反应(RT-PCR)和Western blot检测11例肝癌组织、癌旁组织和正常肝组织中HMGB 1 mRNA和蛋白的表达。此外,HMGB 1蛋白表达与161 HCC的临床病理特征和生存率进行了分析,通过免疫组化。采用t检验、等级相关、Kaplan-Meier曲线和考克斯比例风险回归模型对数据进行分析。RT-PCR和Westernblot检测结果显示,HMGB 1 mRNA和蛋白在肝癌组织中的表达均显著高于癌旁组织(p < 0.001)和正常肝组织(p < 0.001)。免疫组化结果显示HMGB 1在42.9%(69/161)的HCC组织中呈高表达。HMGB 1的高表达与包膜不完全(p = 0.035)和晚期TNM分期(p = 0.036)显著相关。多因素分析显示HMGB 1高表达是影响总生存期(p = 0.009,HR = 1.834,95%CI:1.167-2.881)和无病生存期(p = 0.018,HR = 1.622,95%CI:1.088-2.419)的独立预后因素,沿着肿瘤大小。亚组分析显示,HMGB 1高表达仅预测肿瘤>5 cm的总生存率较差(p = 0.031),但不预测肿瘤≤5 cm的总生存率(p = 0.101)。HMGB 1蛋白可能参与了肝癌的恶性进展,HMGB 1高表达预示肝癌根治性切除术后预后不良,尤其是肿瘤> 5cm的患者。
High mobility group box 1(HMGB1) overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in hepatocellular carcinoma (HCC) remains unclear. The aim of present study was to analyze HMGB1 protein expression in tumor, para-tumor and normal tissue and to assess its prognostic significance for HCC after curative hepatectomy. The levels of HMGB1 mRNA and protein in tumor, para-tumor and normal tissue were evaluated in 11 HCC cases by Reverse Transcription-polymerase chain reaction (RT-PCR) and Western blot. Additionally, HMGB1 protein expression in 161 HCC was analyzed by immunohistochemistry and correlated with clinicopathological characteristics and survivals. Student’s t-test, spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. By RT-PCR and Western blot, the levels of HMGB1 mRNA and protein were significantly higher in HCC, compared to that in para-tumor (p < 0.001) and normal tissue (p < 0.001). Immunohistochemical staining revealed that high expression of HMGB1 was detected in 42.9% (69/161) HCC cases. High expression of HMGB1 was significantly associated with incomplete encapsulation (p = 0.035) and advanced TNM stage (p = 0.036). Multivariate analysis showed that high expression of HMGB1 was an independent prognostic factor for both overall (p = 0.009, HR = 1.834, 95%CI: 1.167-2.881) and disease-free survival (p = 0.018, HR = 1.622, 95%CI: 1.088-2.419), along with tumor size. Subgroup analysis revealed that high expression of HMGB1 predicted poorer overall survival only for tumor >5 cm (p = 0.031), but not for tumor ≤5 cm (p = 0.101). HMGB1 protein might contribute to the malignant progression of HCC, high expression of HMGB1 predicts poor prognosis for patients with HCC after curative hepatectomy, especially for patients with tumor >5 cm.
DOI: 10.1038/nature00858
发表时间: 2002-07-11
期刊: NATURE
影响因子: 64.8
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