Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China ; Department of Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
PLoS One. 2014 Feb 19;9(2):e89097. doi: 10.1371/journal.pone.0089097. eCollection 2014.
High-mobility group box 1 protein (HMGB1) is an evolutionarily ancient and critical regulator of cell death and survival. HMGB1 is a chromatin-associated nuclear protein molecule that triggers extracellular damage. The expression of HMGB1 has been reported in many types of cancers, but the role of HMGB1 in hepato cellular carcinoma (HCC) is unknown.The aim of this study was to analyze the roles of HMGB1 in HCC progression using HCC clinical samples. We also investigated the clinical outcomes of HCC samples with a special focus on HMBG1 expression. In an immunohistochemical study conducted on 208 cases of HCC, HMGB1 had high expression in 134 cases(64.4%).The HMGB1 expression level did not correlate with any clinicopathological parameters, except alpha fetoprotein (AFP) (p = 0.041) and CLIP stage (p = 0.007). However, survival analysis showed that the group with HMBG1 overexpression had a significantly shorter overall survival time than the group with a down-regulated expression of HMBG1 (HR = 0.568, CI (0.398, 0.811), p = 0.002). Multivariate analysis showed that HMGB1 expression was a significant and independent prognostic parameter (HR = 0.562, CI (0.388, 0.815), p = 0.002) for HCC patients. The ability of proliferation, migration and invasion of HCC cells was suppressed with the disruption of endogenous HMGB1 using small interfering RNAs. On the other hand, the ability of proliferation, migration and invasion of HCC cells was strengthened when the expression endogenous HMGB1 was enhanced using HMGB1 DNA. HMGB1 expression may be a novel and independent predictor for the prognosis of HCC patients. The overexpression of HMGB1 in HCC could be a novel, effective, and supplementary biomarker for HCC, since it plays a vital role in the progression of HCC.
高迁移率族蛋白 B1（HMGB1）是细胞死亡和存活的一种古老而关键的调节因子。HMGB1 是一种与染色质相关的核蛋白分子，可引发细胞外损伤。已经在许多类型的癌症中报道了 HMGB1 的表达，但 HMGB1 在肝细胞癌（HCC）中的作用尚不清楚。本研究旨在使用 HCC 临床样本分析 HMGB1 在 HCC 进展中的作用。我们还研究了 HCC 样本的临床结果，特别关注 HMGB1 的表达。在对 208 例 HCC 进行的免疫组织化学研究中，HMGB1 在 134 例（64.4％）中高表达。HMGB1 的表达水平与任何临床病理参数均无关，除甲胎蛋白（AFP）（p = 0.041）和 CLIP 分期（p = 0.007）外。但是，生存分析表明，HMGB1 过表达组的总生存时间明显短于 HMGB1 下调组（HR = 0.568，CI（0.398，0.811），p = 0.002）。多因素分析表明，HMGB1 表达是 HCC 患者的一个显著且独立的预后参数（HR = 0.562，CI（0.388，0.815），p = 0.002）。使用小干扰 RNA 破坏内源性 HMGB1 可抑制 HCC 细胞的增殖，迁移和侵袭能力。另一方面，当使用 HMGB1 DNA 增强内源性 HMGB1 的表达时，可增强 HCC 细胞的增殖，迁移和侵袭能力。HMGB1 表达可能是 HCC 患者预后的新的独立预测因子。HMGB1 在 HCC 中的高表达可能是 HCC 的一种新的，有效的，补充性的生物标志物，因为它在 HCC 的进展中起着至关重要的作用。
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