Overexpression of high-mobility group box 1 correlates with tumor progression and poor prognosis in human colorectal carcinoma
Overexpression of high-mobility group box 1 correlates with tumor progression and poor prognosis in human colorectal carcinoma
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DOI：
10.1007/s00432-009-0706-1
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Liu, Guojin
中科院分区：
文献类型：
--
作者：
Yao, Xingjun;Zhao, Gang;Liu, Guojin
高迁移率组框1 （HMGB1）参与多种重要的生物学过程，包括转录、DNA修复、V(D)J重组、分化、发育和细胞外信号传导。HMGB1在结直肠癌（CRC）中表达升高。然而，HMGB1与CRC患者的临床病理特征，包括生存率的相关性尚未见报道。在本研究中，我们通过免疫组织化学分析研究了HMGB1在结直肠癌中的表达及其预后意义，共使用192份结直肠癌档案石蜡包埋样本。此外，通过siRNA敲低技术破坏内源性HMGB1蛋白，研究HMGB1在肿瘤侵袭和转移过程中的可能作用。55.7%的病例HMGB1过表达。统计分析显示HMGB1表达与结直肠癌患者肿瘤侵袭（P = 0.048）、淋巴结转移（P = 0.011）、远处转移（P = 0.031）、Duke分期（P = 0.029）呈正相关。HMGB1高表达的患者总生存时间较短，而HMGB1低表达的患者总生存时间较长。多因素分析提示HMGB1表达可能是结直肠癌患者生存的独立预后指标。通过siRNA敲低技术破坏内源性HMGB1蛋白可显著抑制SW620细胞的侵袭能力。我们的研究结果表明HMGB1蛋白是CRC患者进展的一个有价值的标志物。高HMGB1表达与CRC患者的总生存率低相关。
High-mobility group box 1 (HMGB1) has been implicated in a variety of biologically important processes, including transcription, DNA repair, V(D)J recombination, differentiation, development, and extracellular signaling. The increased expression of HMGB1 has been described in colorectal cancer (CRC). However, there is no report about the correlation of HMGB1 with clinicopathologic features, including the survival of patients with CRC.In present study, we investigated HMGB1 expression and its prognostic significance in CRC by performing immunohistochemical analysis, using a total of 192 paraffin-embedded archival CRC samples. Moreover, disruption of endogenous HMGB1 protein through a siRNA knockdown technique was performed to investigate the possible role of HMGB1 in the process of tumor invasion and metastasis.Overexpression of HMGB1 was shown in 55.7% cases. Statistical analysis showed that HMGB1 expression was positively correlated with tumor invasion (P = 0.048), lymph node metastasis (P = 0.011), distant metastasis (P = 0.031), and Duke's stage (P = 0.029) of CRC patients. Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival. Multivariate analysis suggested that HMGB1 expression might be an independent prognostic indicator for the survival of patients with CRC. Disruption of endogenous HMGB1 protein through a siRNA knockdown technique was shown to suppress substantially the invasion ability of SW620 cells.Our results suggest that HMGB1 protein is a valuable marker for progression of CRC patients. High HMGB1 expression is associated with poor overall survival in patients with CRC.