Igarashi Hirotaka, Aoyagi Yutaka, Suda Takeshi, Mita Yuhsaku, Kawai Kohichi
Division of Gastroenterology and Hepatology, Department of Cellular Function, Course for Molecular and Cellular Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 757 Asahimachi Dori-1-Bancho, 951-8122, Niigata, Japan
Hepatol Res. 2003 Dec;27(4):280-288. doi: 10.1016/s1386-6346(03)00266-3.
Our previous results showed that the fucosylation index (FI) was considered to be a useful prognostic factor in patients with hepatocellular carcinoma (HCC). On the other hand, serum concentrations of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were regarded as prognostic indicators. However, the relationship among FI, AFP, and DCP as prognostic factors remained unknown. The aim of this study was to elucidate the correlation among these three prognostic factors. One hundred and seventy-six patients with HCC from 1990 to 1998, who showed increment of serum AFP concentrations more than 30ng/ml before treatment, were examined in the present study. FI was determined in these patients by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. FI of AFP was defined as the percentage of the L. culinaris agglutinin (LCA)-reactive species in total AFP (same as L3 fraction). Serum concentrations of DCP were also measured. Enrolled patients with HCC underwent transcatheter arterial embolization, chemoembolization, percutaneous ethanol injection, and/or percutaneous microwave coagulation therapy. The current patients status was the one which was confirmed at the end of March 2001. Analysis by the Cox's proportional hazards model showed that FI, AFP, and DCP were significant prognostic factors. When the tentative demarcation levels of FI, AFP, and DCP were set at 18%, 200ng/ml, and 0.06arbitrary units (AU)/ml, respectively, the following results for the prognostication of patients with HCC were obtained. First, the survival rates in the groups with one out of the three optional markers over the demarcation level were significantly lower than the survival rates of other groups, whose optional one marker was equal to or less than the demarcation level, respectively. Next, the survival rates in the groups in which two out of three optional markers were over the demarcation levels were lower than the survival rates of other groups, whose optional two markers were equal to or less than the demarcation levels, with high significance. On the contrary, there was absence or attenuation of statistically significant differences in the survival rates between the groups in which two of the three optional markers showed no accordant results (high FI and low AFP versus low FI and high AFP, low FI and high DCP versus high FI and low DCP, high DCP and low AFP versus low DCP and high AFP). Finally, we compared the survival rates between the HCC groups, whose optional one marker was over the demarcation level and whose remainders were equal to or less than the demarcation levels and another HCC group whose optional one marker was equal to or less than the demarcation level and whose remainders were over the demarcation levels to reconfirm the weight of each prognostic factor. These comparisons together with Cox's analysis showed that the weight of each prognostic factor in the survival rates is consecutively ordered as DCP, FI, and AFP. The present study indicates that measurements of FI, AFP, and DCP from the sera before the initial treatment improve prognostic estimates and appraisal of the therapeutic outcome in patients with HCC.
我们之前的研究结果表明,岩藻糖基化指数(FI)被认为是肝细胞癌(HCC)患者有用的预后因素。另一方面,血清甲胎蛋白(AFP)和异常凝血酶原(DCP)浓度被视为预后指标。然而,FI、AFP和DCP作为预后因素之间的关系仍不清楚。本研究的目的是阐明这三种预后因素之间的相关性。本研究对1990年至1998年期间176例HCC患者进行了检查,这些患者在治疗前血清AFP浓度升高超过30ng/ml。通过在存在刀豆凝集素的情况下进行交叉免疫亲和电泳来测定这些患者的FI。AFP的FI定义为刀豆凝集素(LCA)反应性物质在总AFP(与L3组分相同)中的百分比。还测量了DCP的血清浓度。入选的HCC患者接受了经导管动脉栓塞、化疗栓塞、经皮乙醇注射和/或经皮微波凝固治疗。目前患者的状况是在2001年3月底确认的状况。通过Cox比例风险模型分析表明,FI、AFP和DCP是显著的预后因素。当将FI、AFP和DCP的暂定分界水平分别设定为18%、200ng/ml和0.06任意单位(AU)/ml时,获得了以下HCC患者预后的结果。首先,三个可选标志物中有一个超过分界水平的组的生存率显著低于其他组,其他组的可选一个标志物分别等于或低于分界水平。其次,三个可选标志物中有两个超过分界水平的组的生存率低于其他组,其他组的可选两个标志物等于或低于分界水平,具有高度显著性。相反,三个可选标志物中有两个结果不一致的组(高FI和低AFP与低FI和高AFP、低FI和高DCP与高FI和低DCP、高DCP和低AFP与低DCP和高AFP)之间的生存率在统计学上没有显著差异或差异减弱。最后,我们比较了一个可选标志物超过分界水平而其余标志物等于或低于分界水平的HCC组与另一个可选一个标志物等于或低于分界水平而其余标志物超过分界水平的HCC组之间的生存率,以再次确认每个预后因素的权重。这些比较与Cox分析一起表明,每个预后因素在生存率中的权重依次为DCP、FI和AFP。本研究表明,在初始治疗前从血清中测量FI、AFP和DCP可改善HCC患者的预后估计和治疗结果评估。