AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma

AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma
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DOI:
10.1097/01.sla.0000234840.74526.2b
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发表时间:
2006-09-01
期刊:
影响因子:
9
通讯作者:
Todo, Satoru
Todo, Satoru
中科院分区:
医学1区
文献类型:
--
作者:
Kamiyama, Toshiya;Takahashi, Masato;Todo, Satoru

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目的:探讨实时定量逆转录聚合酶链式反应(RT-PCR)靶向甲胎蛋白(AFP)信使核糖核酸(AFP)检测肝细胞癌(简称肝癌)根治性切除前后的复发和患者生存情况。术前抽吸骨髓,以甲胎蛋白(AFP)为靶分子,对手术前后采集的外周血进行实时定量RT-PCR分析。中位随访期为23个月(6~54个月)。比较AFP mRNA阳性和阴性患者的患者生存期(PS)、无病生存期(DFS)和临床病理特征。结果:24例患者死亡,其中22例死于肝癌。肝细胞癌复发66例,其中肝性37例(56.1%),远端17例(25.8%),远端12例(18.2%)。骨髓AFP mRNA阳性38例(27.9%),阴性98例(72.1%)。1年和3年生存率分别为96.6%和91.4%,AFP mRNA阴性分别为86.2%和55.5%(P<0.0001)。AFP mRNA阴性患者1年和3年DFS分别为73.2%和44.8%,AFP mRNA阳性患者分别为54.5%和25.8%(P=0.0399)。单因素分析显示,门静脉侵犯、肿瘤大小、多发肿瘤、肿瘤分化程度与下PS和DFS相关。多因素分析显示,AFP mRNA阳性是PS(P=0.001)和DFS(P=0.0165)的最重要危险因素。结论:围手术期外周血和体循环中AFP mRNA的表达可预测肝细胞癌根治性肝切除术后患者的生存和复发。
Objective: To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival.Summary Background Data: The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome.Methods: Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA.Results: Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS.Conclusion: AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.