高迁移率族蛋白 B1（HMGB1）高表达预示着根治性肝切除术后肝细胞癌预后不良。
High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy.
机构信息
Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-Sen University, 651 Dongfeng Road East, Guangzhou, 510060, China.
出版信息
J Transl Med. 2012 Jul 2;10:135. doi: 10.1186/1479-5876-10-135.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
背景
高迁移率族蛋白 1（HMGB1）在多种人类癌症中过度表达。然而，HMGB1 在肝细胞癌（HCC）中的作用仍不清楚。本研究旨在分析肿瘤、癌旁和正常组织中 HMGB1 蛋白的表达，并评估其在根治性肝切除术后对 HCC 的预后意义。
方法
通过逆转录-聚合酶链反应（RT-PCR）和 Western blot 评估 11 例 HCC 患者肿瘤、癌旁和正常组织中 HMGB1mRNA 和蛋白的水平。此外，采用免疫组织化学方法分析 161 例 HCC 中 HMGB1 蛋白的表达，并与临床病理特征和生存相关。采用 Student's t 检验、Spearman 秩相关、Kaplan-Meier 图和 Cox 比例风险回归模型进行数据分析。
结果
通过 RT-PCR 和 Western blot，HMGB1mRNA 和蛋白的水平在 HCC 中明显高于癌旁（p<0.001）和正常组织（p<0.001）。免疫组织化学染色显示，69/161（42.9%）例 HCC 中 HMGB1 高表达。HMGB1 高表达与不完全包膜（p=0.035）和晚期 TNM 分期（p=0.036）显著相关。多因素分析显示，HMGB1 高表达是总生存（p=0.009，HR=1.834，95%CI：1.167-2.881）和无病生存（p=0.018，HR=1.622，95%CI：1.088-2.419）的独立预后因素，与肿瘤大小有关。亚组分析显示，HMGB1 高表达仅预测肿瘤>5cm 的患者总体生存较差（p=0.031），而肿瘤≤5cm 的患者则无此预测作用（p=0.101）。
结论
HMGB1 蛋白可能有助于 HCC 的恶性进展，HMGB1 高表达预示根治性肝切除术后 HCC 患者预后不良，尤其是肿瘤>5cm 的患者。
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