・临床研究・肝细胞生长因子及其受体c2met在肝细胞癌中的表达与预后价值吴福生 郑树森 吴灵娇 丁伟 马志敏 王照明 滕理送 赵文和 【摘要】 目的 研究肝癌切除前、后血清肝细胞生长因子(HGF)的动态变化及其受体c2met在癌组织中的表达,探讨HGF/c2met对手术切除后肝癌患者的预后价值。
方法 收集手术切除的25例肝细胞癌患者血清及组织标本,用酶联免疫法(E L I S A)测定术前1d、术后第3、7、10天血清HGF浓度,分别用免疫组织化学及逆转录聚合酶链反应(RT2PCR)方法检测肝癌及癌旁组织中c2met蛋白及mRNA的表达。
分析术前血清HGF水平及癌组织中c2met表达程度与不同临床病理因素之间的关系及影响手术后血清HGF水平变化的因素。
以20例健康献血员为正常对照组,22例慢性乙型肝炎患者及22例乙型肝炎肝硬化肝功能失代偿(Child B或C级)患者作为慢性乙肝组和肝硬化失代偿组。
结果 肝癌患者血清HGF浓度高于正常对照组及慢性乙肝组[(1103±0109)ng/m l比(0169±0102)、(0174±0109)ng/m l,P<0105],但与肝硬化失代偿组[(1104±0111)ng/m l]比较差异无统计学意义。
术后HGF浓度上升高峰出现在术后第3天,术后第7、10天逐渐下降,但仍高于正常水平。
术前、术后各组的血清HGF组间比较,仅术后第3天组差异有统计学意义。
影响术前血清HGF水平的主要因素有:肿瘤直径>5c m、伴有结节肝硬化、门静脉癌栓、术前血清甲胎蛋白(AFP)≥400μg/L。
从术前到术后第3天,大区段切除比小区段切除者的血清HGF浓度上升更明显(P=01047)。
中度和强阳性c2met蛋白表达在肝癌组织中(21/25)明显高于癌旁组织(5/25)。
高表达的c2met mRNA见于所有肝癌组织中,在癌旁组织中仅6例有高表达。
癌组织中c2met蛋白表达的强度与有无合并门静脉癌栓有关,与肿瘤大小、血清AFP水平、血清HGF水平、有无肝硬化及肝癌的分化程度无相关性。
但在癌旁组织,合并肝硬化组c2met蛋白表达高于无肝硬化组。
术后有肿瘤复发或转移的病例,其术前血清HGF水平及肿瘤组织中c2met蛋白表达显著高于无复发或转移的病例。
HGF水平与肿瘤组织中c2met表达无相关性。
结论 肝癌患者有血清HGF及癌组织中c2met的高表达,术后血清HGF的持续升高可能与肝癌的早期复发和转移有关。
【关键词】 癌,肝细胞; 肝细胞生长因子; 原癌基因蛋白质c2met; 肝切除术Study on the prognosti c va lue of hepa tocyte growth factor and c2m et for pa ti en ts w ith hepa tocellul arcarc i n o ma WU Fu2sheng3,ZHEN G Shu2sen,WU L ing2jiao,D I N G W ei,MA Zhi2m in,WAN G Zhao2m ing,TEN G L i2song,ZHAO W en2he.3D epart m ent of Surgical O ncology,First A ffiliated Hospital,ZhejiangU niversity School of M edicine,Hangzhou310003,ChinaCorresponding author:WU L ing2jiao,Em ail:1020w lj@1631co m【Abstract】 O bjecti ve To analyze the p r ognostic value of hepat ocyte gr owth fact or(HGF)andc2met for patients with hepat ocellular carcinoma(HCC)after hepatect omy1M ethods T wenty2five patientsundergoing partial hepatect omy for HCC were studied1Seru m HGF level was deter m ined using E L I S A kitbef ore and after operati on res pectively1c2met p r otein and mRNA exp ressi on in cancer ous and paracancer oustissues were detected by i m munohist oche m ical and RT2PCR methods res pectively1The correlati ons ofclinical2pathol ogic para meters with the HGF level in seru m and c2met exp ressi on in cancer ous tissue wereanalyzed res pectively1Results HCC patients had a significantly higher concentrati on of seru m HGF thannor mal contr ols and chr onic hepatitis B res pectively[(1103±0109)ng/m l vs(0169±0102)ng/m l and(0174±0109)ng/m l]1No significant difference in seru m HGF was observed bet w een HCC and cirrhosis基金项目:浙江省科技攻关计划项目(2004C30074)作者单位:310003杭州,浙江大学医学院附属第一医院肿瘤外科(吴福生、马志敏、滕理送、赵文和),肝胆胰外科暨器官移植中心(郑树森),传染病研究所(吴灵娇),病理科(丁伟、王照明)通讯作者:吴灵娇,Email:1020wlj@patients with Child2Pugh score B/C[(1103±0109)ng/m l vs(1104±0111)ng/m l]1Seru m HGF concentrati ons were positively correlated with tu mor size(>5c m),node cirrhosis,portal vein tu mor thr o mbi(P VTT)and p reoperativeα2fet op r otein(AFP)level(≥400μg/L)1After the resecti on of tu mor, seru m HGF concentrati on had a peak on the third post operative day(P OD),and then declined,but did not return t o nor mal level on the tenth P OD1Fr om p reoperative day t o third P OD,HGF concentrati on had a higher elevati on in patients with maj or resecti on than with l ocal resecti on1Moderately or str ongly positive exp ressi on of c2met p r otein was observed in21cancer ous regi ons(21/25),and only in5paracancer ous regi ons1The intensive exp ressi on of c2met mRNA was100%(25/25)detectable in the cancer ous tissues, but only24%(6/25)in the paracancer ous tissues1The exp ressi on extent of c2met p r otein was correlated with portal vein tu mor thr ombi(P VTT)1I n paracancer ous tissues,the exp ressi on of c2met p r otein was more intense in patients with cirrhosis than those without cirrhosis1The patientswith recurrence or metastases after operati on had a higher level of seru m HGF and more intensive exp ressi on of c2met than other patients1No significant ass ociati on was observed bet w een HGF in seru m and c2met exp ressi on in cancer ous tissue1 Conclusi on s The over2exp ressi on of HGF and its recep t or c2met indicate an adverse p r ognosis for HCC patients1The sustained high level of seru m HGF after hepatect omy may be a fact or related t o early tu mor recurrence and metastasis1【Key words】 Carcinoma,hepat ocellular; Hepat ocyte gr owth fact or; Pr ot o2oncogene p r otein c2met; Hepatect omy 肝细胞生长因子(HGF)最早是从肝部分切除的大鼠血清中分离得到,是一种很强的刺激肝细胞增殖的分裂原,其受体c2met主要在各种上皮细胞中表达[1,2]。