Wu F, Wu L, Zheng S, Ding W, Teng L, Wang Z, Ma Z, Zhao W
Department of Surgical Oncology, First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, China.
Dig Liver Dis. 2006 Jul;38(7):490-7. doi: 10.1016/j.dld.2006.03.007. Epub 2006 Apr 14.
To study the dynamic change of hepatocyte growth factor after hepatectomy in patients with primary liver cancer, and to analyse the prognostic value of hepatocyte growth factor and c-met for these patients.
Thirty-one consecutive patients undergoing partial hepatectomy for liver cancer were studied. Serum hepatocyte growth factor level was determined by using enzyme-linked immunosorbent assay kit before and after operation, respectively. C-met protein and MRNA expressions in cancerous and paracancerous tissues were examined by immunohistochemical and RT-PCR methods, respectively. The correlations between clinical-pathologic parameters and the expressions of hepatocyte growth factor in serum and c-met in cancerous tissues were analysed, respectively.
Liver cancer patients had a significantly higher level of serum hepatocyte growth factor than normal controls (1.0424+/-0.498 ng/ml versus 0.685+/-0.115 ng/ml, p=0.008). Serum hepatocyte growth factor level was positively affected by tumour size, node cirrhosis, portal vein tumour thrombi, cholangiocarcinoma (including combined hepatocellular carcinoma), poorly differentiated hepatocellular carcinoma and tumour recurrence or metastases. After hepatectomy, serum hepatocyte growth factor level peaked on the third postoperative day, and then declined, but did not return to normal level on the postoperative day 10. From the preoperative day to postoperative day 10, the level of serum hepatocyte growth factor had a decrease of percent (85.33+/-10.2%) in the group with large tumours (>5 cm), but an elevation of percent (121.9+/-10.3%) in the group with small tumours (<or=5 cm). From the preoperative day to postoperative day 3, the level of serum hepatocyte growth factor had a higher elevation in the group with major resection than in the group with local resection (p=0.016). Moderately or strongly positive expression of c-met protein was observed in 27 cancerous regions (27/31), and only in 5 paracancerous regions. The intensive expression of c-met MRNA was 100% (31/31) detectable in the cancerous tissues, but only 22.6% (7/31) in the paracancerous tissues. C-met protein expression in cancerous tissues was correlated with portal vein tumour thrombi, cholangiocarcinoma and tumour recurrence or metastases, and the expression in paracancerous tissues was correlated with node cirrhosis. No significant correlation was observed between the hepatocyte growth factor in serum and c-met in cancerous tissues.
The over-expressions of the hepatocyte growth factor and c-met indicates an adverse prognosis for patients with liver cancer. The sustained high level of serum hepatocyte growth factor after hepatectomy may be a factor related to early tumour recurrence and metastasis. Liver regeneration may be a main factor leading to high level of serum hepatocyte growth factor in early postoperative stage.
研究原发性肝癌患者肝切除术后肝细胞生长因子的动态变化，并分析肝细胞生长因子和c-met对这些患者的预后价值。
对31例连续接受肝癌部分肝切除术的患者进行研究。分别在手术前后使用酶联免疫吸附测定试剂盒测定血清肝细胞生长因子水平。分别采用免疫组织化学和RT-PCR方法检测癌组织和癌旁组织中c-met蛋白和mRNA的表达。分别分析临床病理参数与血清中肝细胞生长因子表达及癌组织中c-met表达之间的相关性。
肝癌患者血清肝细胞生长因子水平显著高于正常对照组（1.0424±0.498 ng/ml对0.685±0.115 ng/ml，p = 0.008）。血清肝细胞生长因子水平受肿瘤大小、结节性肝硬化、门静脉癌栓、胆管癌（包括合并肝细胞癌）、低分化肝细胞癌及肿瘤复发或转移的正向影响。肝切除术后，血清肝细胞生长因子水平在术后第3天达到峰值，然后下降，但术后第10天未恢复至正常水平。从术前到术后第10天，大肿瘤组（>5 cm）血清肝细胞生长因子水平下降百分比为（85.33±10.2%）,而小肿瘤组（≤5 cm）则升高百分比为（121.9±10.3%）。从术前到术后第3天，大切除组血清肝细胞生长因子水平升高幅度高于局部切除组（p =
0.016）。在27个癌区（27/31）观察到c-met蛋白中度或强阳性表达，而在仅5个癌旁区域观察到。癌组织中c-met mRNA的强表达在癌组织中可检测率为100%（31/31），而在癌旁组织中仅为22.6%（7/31）。癌组织中c-met蛋白表达与门静脉癌栓、胆管癌及肿瘤复发或转移相关，癌旁组织中的表达与结节性肝硬化相关。血清中肝细胞生长因子与癌组织中c-met之间未观察到显著相关性。
肝细胞生长因子和c-met的过表达提示肝癌患者预后不良。肝切除术后血清肝细胞生长因子持续高水平可能是与早期肿瘤复发和转移相关的一个因素。肝再生可能是术后早期血清肝细胞生长因子水平升高的主要因素。
