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目的探讨C5L2表达在肝细胞肝癌(hepatocellular carcinoma,HCC)患者预后判断中的价值。方法回顾性分析2012年10月至2013年9月在复旦大学附属中山医院接受根治性切除术的175例原发性HCC患者。研究C5L2表达与临床基本参数之间的关系,运用COX回归模型分析各临床参数对术后复发的影响,通过Kaplan-Meier法评估C5L2和AFP联合应用的预后判断效能。在5种肝癌细胞系中检测C5L2表达,筛选Hep3B和Huh7分别对C5L2进行下调和上调,检测细胞侵袭迁移能力的改变并初步探索其机制。结果 C5L2表达与性别、肿瘤大小和复发相关,C5L2低表达患者复发率更高,多因素分析显示C5L2低表达是肝癌复发的独立危险因素,C5L2和AFP联合应用可以更加有效地判断肝癌预后。在Hep3B中敲除C5L2可促进细胞侵袭迁移,伴随β-catenin和MMP2表达上调;相反,在Huh7中过表达C5L2可抑制细胞侵袭迁移,伴随β-catenin和MMP2表达下调。结论 C5L2可作为判断肝癌预后的辅助指标,帮助临床制定更有效的HCC治疗和监测方案。
Objective To investigate the value of C5L2 expression in the prognosis of patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis of 175 patients with primary HCC undergoing radical resection at Zhongshan Hospital affiliated to Fudan University from October 2012 to September 2013 was performed. The relationship between C5L2 expression and clinical parameters was studied. The effect of clinical parameters on postoperative recurrence was analyzed by COX regression model. The prognosis of C5L2 and AFP was assessed by Kaplan-Meier method. C5L2 expression was detected in five hepatocellular carcinoma cell lines, and Hep3B and Huh7 were screened for down-regulation and up-regulation of C5L2 respectively. The invasion and migration of cells were detected and the mechanism was explored. Results C5L2 expression was associated with gender, tumor size and recurrence, and the recurrence rate was higher in patients with low expression of C5L2. Multivariate analysis showed that low expression of C5L2 was an independent risk factor for recurrence of liver cancer. Combined application of C5L2 and AFP could be more effective in predicting the prognosis of liver cancer. Knockdown of C5L2 in Hep3B promoted cell invasion and migration with increased expression of β-catenin and MMP2. In contrast, overexpression of C5L2 in Huh7 inhibited cell invasion and migration with down-regulation of the expression of β-catenin and MMP2. Conclusion C5L2 can be used as an auxiliary index to judge the prognosis of HCC, and help to develop a more effective HCC treatment and monitoring plan.