复旦863项目癌症新靶位文章登Hepatology

生物通报道，复旦大学附属中山医院肝癌研究所，复旦大学生物医学研究所的科学家在最新 一期的肝病权威杂志《Hepatology》杂志上发表文章，解析肝癌患者介绍肝移植治疗后的癌细胞转移生物标记。

　　

生物通报道，复旦大学附属中山医院肝癌研究所，复旦大学生物医学研究所的科学家在最新 一期的肝病权威杂志《Hepatology》杂志上发表文章，介绍肝移植治疗后的癌细胞转移生物标记。

 

文章通讯作者是复旦大学樊嘉教授，樊嘉教授现任中山医院副院长，肝外科主任，其领衔的项目“肝癌门静脉肺癌栓形成机制及多模式综合治疗技术”刚刚获得2008年度国家科技进步二等奖。去年，樊嘉教授曾在Cancer Research上发表肝癌研究成果，了解详情点击：http://www.ebiotrade.com/newsf/2008-11/20081120164128.htm。

 

在2月份的《Hepatology》发表的文章中，樊嘉教授关注肝细胞癌患者肝移植手术后的复发问题。肝细胞癌（hepatology carcinoma，HCC）是一种恶性的侵袭性癌症，对于不可用肝切除术来治疗的肝细胞癌患者来说最佳的治疗手段是进行肝脏移植。然而，不幸的是，有些肝细胞癌患者在接受肝移植后往往出现癌细胞转移扩散的情况，这大大降低了患者的寿命。

 

为了鉴定与癌细胞转移扩散相关的蛋白，樊嘉领衔的研究小组对接受肝移植术的肝细胞癌患者进行跟踪随访，随访的患者包括有肝癌复发者和未复发者。研究小组鉴定出149种蛋白，其中一种名为钙蛋白酶小亚基1（calpain small subunit，Capn4）引起了研究者的关注，它是一种与多种癌细胞转移扩散相关蛋白有相互作用的蛋白。

 

研究发现Capn4在肝移植后的复发患者中的表达量很高，并且在体外实验中研究发现Capn4具有增强癌细胞转移的能力。研究小组用siRNA阻断肝癌细胞中Capn4基因的表达，结果发现可极大地降低癌细胞的扩散性和侵袭性。用组织芯片技术进行调查发现，192例具有癌细胞转移特性的肝癌患者细胞中Capn4都过度表达，单变量和多变量分析发现Capn4是一个可预测肝细胞癌患者预后情况（复发和存活时间）的独立指标。

 

研究者得出结论，Capn4不仅可成为肝癌复发和预后的诊断生物标记，还可能成为具有潜力的治疗靶位。（生物通 小茜）

 

生物通推荐原文检索：Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma

【Abstract】

Liver transplantation (LT) is one of the best therapeutic options for nonresectable hepatocellular carcinoma (HCC). Unfortunately, some HCC patients succumb to the disease after LT, which reduces long- and medium-term survival. To identify the proteins associated with HCC invasion and metastasis, HCC patients undergoing LT with complete follow-up data were included in this study and were categorized into recurrence and nonrecurrence groups. We extracted the total protein from the acquired homogeneous tumor cells and applied a cleavable isotope-coded affinity tag technology to quantitate relative changes in protein levels between the two groups. We identified a total of 149 proteins with two-dimensional liquid chromatography coupled with tandem mass spectrometry, including 52 differentially expressed proteins by at least two-fold. Among them, calpain small subunit 1 (Capn4), a protein with relevant interactions with many migration-invasion-related proteins, has attracted more attention. First, Capn4 overexpression in the recurrence group was confirmed via real-time polymerase chain reaction and western blotting in another cohort of 40 HCC patients undergoing LT. Second, Capn4 was associated with enhanced invasiveness in vitro. The small interfering RNA-mediated knockdown expression of Capn4 in HCC cell lines significantly inhibited its mobile and invasive ability. Tissue microarray in a further 192 cases revealed that Capn4 significantly correlated with invasive phenotype of HCC, and univariate and multivariate analyses indicated that Capn4 is an independent prognostic factor for recurrence and survival of HCC patients. Conclusion: Our study revealed that Capn4 overexpression underlies invasion and metastasis after LT for HCC and might be a candidate biomarker for future diagnosis and a target for therapy. （生物通）

 

樊嘉，1958年出生，复旦大学附属中山医院副院长，肝癌研究所及肝外科主任，复旦大学器官移植中心副主任，中华医学会外科学会肝脏学组委员，美国肿瘤外科学会会员，国际肝胆胰协会委员。擅长肝胆胰外科及肝移植手术，主持并成功施行了全国首例劈离式肝移植术，创造了国内肝移植年龄最大和最小纪录。