復(fù)旦大學(xué)附屬中山醫(yī)院肝癌研究所,，復(fù)旦大學(xué)生物醫(yī)學(xué)研究所的科學(xué)家在最新 一期的肝病權(quán)威雜志Hepatology雜志上發(fā)表文章,，解析肝癌患者介紹肝移植治療后的癌細(xì)胞轉(zhuǎn)移生物標(biāo)記,。
在2月份的Hepatology發(fā)表的文章中,，樊嘉教授關(guān)注肝細(xì)胞癌患者肝移植手術(shù)后的復(fù)發(fā)問題,。肝細(xì)胞癌（hepatology carcinoma,，HCC）是一種惡性的侵襲性癌癥,，對于不可用肝切除術(shù)來治療的肝細(xì)胞癌患者來說最佳的治療手段是進行肝臟移植,。然而，不幸的是,，有些肝細(xì)胞癌患者在接受肝移植后往往出現(xiàn)癌細(xì)胞轉(zhuǎn)移擴散的情況,，這大大降低了患者的壽命。
為了鑒定與癌細(xì)胞轉(zhuǎn)移擴散相關(guān)的蛋白,，樊嘉領(lǐng)銜的研究小組對接受肝移植術(shù)的肝細(xì)胞癌患者進行跟蹤隨訪,，隨訪的患者包括有肝癌復(fù)發(fā)者和未復(fù)發(fā)者。研究小組鑒定出149種蛋白,，其中一種名為鈣蛋白酶小亞基1（calpain small subunit,，Capn4）引起了研究者的關(guān)注，它是一種與多種癌細(xì)胞轉(zhuǎn)移擴散相關(guān)蛋白有相互作用的蛋白,。
研究發(fā)現(xiàn)Capn4在肝移植后的復(fù)發(fā)患者中的表達量很高,，并且在體外實驗中研究發(fā)現(xiàn)Capn4具有增強癌細(xì)胞轉(zhuǎn)移的能力。研究小組用siRNA阻斷肝癌細(xì)胞中Capn4基因的表達,，結(jié)果發(fā)現(xiàn)可極大地降低癌細(xì)胞的擴散性和侵襲性,。用組織芯片技術(shù)進行調(diào)查發(fā)現(xiàn),，192例具有癌細(xì)胞轉(zhuǎn)移特性的肝癌患者細(xì)胞中Capn4都過度表達，單變量和多變量分析發(fā)現(xiàn)Capn4是一個可預(yù)測肝細(xì)胞癌患者預(yù)后情況（復(fù)發(fā)和存活時間）的獨立指標(biāo),。
研究者得出結(jié)論,，Capn4不僅可成為肝癌復(fù)發(fā)和預(yù)后的診斷生物標(biāo)記，還可能成為具有潛力的治療靶位,。（生物谷Bioon.com）
生物谷推薦原始出處：
Hepatology. 2009 Feb;49(2):460-70.
Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma.
Bai DS, Dai Z, Zhou J, Liu YK, Qiu SJ, Tan CJ, Shi YH, Huang C, Wang Z, He YF, Fan J.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, PR China.
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.
