Zhang Zhao-Yang, Dong Jia-Hong, Chen Yong-Wei, Wang Xian-Qiang, Li Chong-Hui, Wang Jian, Wang Guo-Qiang, Li Hai-Lin, Wang Xue-Dong
Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Asian Pac J Cancer Prev. 2012;13(6):2503-9. doi: 10.7314/apjcp.2012.13.6.2503.
Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.
关于半乳糖凝集素-9与癌症的研究颇多,但关于其与肝细胞癌的关系却知之甚少。在本研究中,我们使用靶向半乳糖凝集素-9的小干扰RNA(siRNA)来下调HepG2细胞中的表达。结果,在半乳糖凝集素-9表达降低后,细胞聚集受到抑制,而细胞的增殖、黏附、对细胞外基质的侵袭、细胞-内皮细胞黏附和跨内皮侵袭等其他行为则明显增强。当通过免疫组织化学检测200例肝细胞癌患者肿瘤中的半乳糖凝集素-9表达时,结合水平与组织病理学分级、淋巴结转移、血管侵袭和肝内转移密切相关(P<0.05)。此外,生存分析表明,半乳糖凝集素-9表达阳性的患者生存时间比阴性患者长得多,对数秩检验表明这种差异具有统计学意义(P<0.0001)。Cox比例风险模型表明,肝细胞癌中半乳糖凝集素-9表达阴性是患者生存的一个重要危险因素。我们认为,半乳糖凝集素-9可能是肝细胞癌患者中具有抗转移潜力的新预后因素。