Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence.
Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence.
复制标题
X连锁凋亡抑制蛋白在肝细胞癌中的表达促进转移和肿瘤复发。
DOI：
10.1002/hep.22393
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发表时间：
2008-08
期刊：
影响因子：
13.5
通讯作者：
Yi, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Shi, Ying-Hong;Ding, Wen-Xing;Zhou, Jian;He, Jun-Yi;Xu, Yang;Gambotto, Andrea A.;Rabinowich, Hannah;Fan, Jia;Yi, Xiao-Ming
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long-term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood. Our initial studies in established HCC cell lines with different metastatic capabilities indicated a correlation of metastasis with the resistance to apoptosis and therefore the ability to survive in stressed conditions. Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to increased metastatic foci in vivo. Furthermore, we found that nearly 90% of clinical samples from advanced HCC patients expressed high levels of XIAP. Patients with XIAP-positive tumors had a significantly increased risk to relapse, which was resulted from metastasis, following total liver resection and orthotopic liver transplantation. Indeed, XIAP expression could be an independent prognostic factor for predicting disease-free survival rate and overall survival rate of these patients. XIAP expression was also highly correlated with advanced cases that exceeded the Milan criteria and could be a prognostic factor for disease-free survival in these patients as well. Conclusion: our studies have revealed an important molecule in controlling HCC metastasis, defined a biomarker that can be utilized to predict HCC recurrence and patient survival following treatment, and suggest that XIAP can be a molecular target subject to intervention to reduce metastasis and recurrence.
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