肝癌患者围手术期外周血甲胎蛋白mRNA表达与术后复发的关系

Correlation of Perioperative Alpha-fetoprotein Expression in Peripheral Blood to Recurrence of Hepatocellular Carcinoma

背景与目的:甲胎蛋白(alpha-fetoprotein,AFP)mRNA是检测肝癌患者外周血中癌细胞常用的标志物。本研究探讨肝癌患者围手术期的外周血中AFPmRNA表达与术后复发的关系。方法:应用巢式PCR和Taq Man MGB探针法PCR定量技术,检测56例肝细胞癌患者术前和术后外周血、15例良性肝占位性病变合并肝硬化患者外周血以及30例健康志愿者外周血AFP mRNA的表达情况。结果:肝癌患者术前外周血AFP mRNA的阳性率为42.9%(24/56),高于良性肝占位合并肝硬化患者的13.3%(2/15)和健康对照的10.0%(3/30),其差异均有统计学意义(P=0.035,P=0.002)。术前AFP mRNA的表达与肿瘤有无肉眼及镜下血管侵犯的相关性有统计学意义(P=0.029,P<0.001)。AFP mRNA阴性患者1、2、3年生存率及无瘤生存率均比AFP mRNA阳性患者术后高(P=0.003,P=0.039)。Cox多因素分析结果显示术前外周血AFP mRNA阳性是预测术后复发的独立因素(P=0.018)。术后患者外周血AFP mRNA的阳性率为37.5%(21/56),术后AFP mRNA的表达与患者各项临床病理特征、预后以及术前AFP mRNA水平的相关性均无统计学意义。结论:肝癌患者术前外周血中AFP mRNA阳性者比AFP mRNA阳性者肿瘤侵袭性更强,术后可能更易复发。

BACKGROUND ＆ OBJECTIVE： Alpha-fetoprotein （AFP）is a marker often used to detect carcinoma cells in peripheral blood of patients with hepatocellular carcinoma （HCC）. This study was to explore the correlation of perioperative AFP expression in peripheral blood to recurrence of HCC. METHODS.. Peripheral blood samples from 56 HCC patients, obtained perioperatively, were tested for the presence of AFP mRNA by nested reverse transcription-polymerase chain reaction （RT-PCR） and TaqMan MGB probe real-time quantitative PCR. The peripheral blood samples from 15 patients with benign liver masses and cirrhosis, and 30 healthy volunteers were used as control. RESULTS. The positive rate of AFP mRNA in preoperative peripheral blood was significantly higher in HCC patients than in patients with benign liver masses and cirrhosis （42.9% vs. 13.3%, P= 0.035） and healthy volunteers （42.9% vs. 10.0%,P=0.002）. The expression of AFP mRNA in preoperative peripheral blood was significantly related to tumor vascular invasion, either observed macroscopically （P=0.029） or microscopically （P〈0.001）. The 1-, 2-, and 3-year overall and disease-free survival rates were significantly higher in AFP-negative patients than in AFP- positive patients （P=0.003, P=0.039）. Cox multivariate analysis showed that preoperative expression of AFP mRNA in peripheral blood was an independent factor for predicting recurrence （P=0.018）. The positive rate of AFP mRNA in postoperative peripheral blood samples from HCC patients was 37.5%. The presence of AFP mRNA in postoperative peripheral blood was not related to any clinicopathologic factors, AFP mRNA levels in preoperative peripheral blood, and prognosis of the HCC patients. CONCLUSION： The presence of AFP mRNA in preoperative peripheral blood is related to tumor invasion of HCC, and may be a predictor maker of tumor recurrence.