Cabrera Roniel, Fitian Asem I, Ararat Miguel, Xu Yiling, Brusko Todd, Wasserfall Clive, Atkinson Mark A, Liu Chen, Nelson David R
Section of Hepatobiliary Diseases, Department of Medicine;
Oncol Lett. 2012 Oct;4(4):840-846. doi: 10.3892/ol.2012.826. Epub 2012 Jul 26.
In a previous study, we showed that the level of soluble CD25 (sCD25) was elevated in a small series of patients with hepatocellular carcinoma (HCC). In the present study, we determined the capacity of serum levels of sCD25 to detect the presence and the early stage of HCC using a larger cohort of HCC patients and evaluated the correlation between sCD25 level and tumor burden. Serum levels of sCD25 were quantified using ELISA in patients with HCC (n=145), controls with advanced fibrosis (n=61) and healthy control subjects (n=30). The levels of sCD25 in patients with HCC (median, 6,955 pg/ml) were significantly higher than those in cirrhosis-only patients (4,310 pg/ml; P<0.0001). At a cut-off value of 2,180 pg/ml, sCD25 had a sensitivity of 92.3% and a specificity of 37.7% in detecting HCC presence [area under the curve (AUC) of 0.685; P<0.0001]. By comparison, α-fetoprotein (AFP) had a sensitivity of 53.8% and a specificity of 86.8% at a cut-off value of 32.8 ng/ml (AUC=0.755; P<0.0001) for HCC presence detection. For early HCC, the sensitivity of sCD25 was 89.6% and its specificity was 39.3% (AUC=0.630; P<0.0001) at a cut-off value of 2,859 pg/ml, while AFP had a sensitivity of 41.7% and a specificity of 82.6% at a cut-off value of 20.6 ng/ml (AUC=0.630; P=0.0257). We also found a significant positive correlation between serum levels of sCD25 and tumor stage. In the present study study, sCD25 was more effective than AFP at detecting the presence and early stages of HCC. This immune factor may hold promise as a novel predictive marker of HCC presence and may be useful in distinguishing early HCC from advanced cirrhosis, currently areas of global unmet need.
在之前的一项研究中,我们发现一小部分肝细胞癌(HCC)患者的可溶性CD25(sCD25)水平升高。在本研究中,我们使用更大的HCC患者队列确定了血清sCD25水平检测HCC存在及早期阶段的能力,并评估了sCD25水平与肿瘤负荷之间的相关性。采用酶联免疫吸附测定法(ELISA)对HCC患者(n = 145)、晚期纤维化对照组(n = 61)和健康对照者(n = 30)的血清sCD25水平进行定量检测。HCC患者的sCD25水平(中位数为6,955 pg/ml)显著高于仅患肝硬化的患者(4,310 pg/ml;P < 0.0001)。在检测HCC存在时,以2,180 pg/ml为临界值,sCD25的灵敏度为92.3%,特异度为37.7% [曲线下面积(AUC)为0.685;P < 0.0001]。相比之下,甲胎蛋白(AFP)在检测HCC存在时,以32.8 ng/ml为临界值,灵敏度为53.8%,特异度为86.8%(AUC = 0.755;P < 0.0001)。对于早期HCC,以2,859 pg/ml为临界值时,sCD25的灵敏度为89.6%,特异度为39.3%(AUC = 0.630;P < 0.0001),而AFP以20.6 ng/ml为临界值时,灵敏度为41.7%,特异度为82.6%(AUC = 0.630;P = 0.0257)。我们还发现血清sCD25水平与肿瘤分期之间存在显著正相关。在本研究中,sCD25在检测HCC的存在及早期阶段方面比AFP更有效。这种免疫因子有望成为HCC存在的新型预测标志物,可能有助于区分早期HCC与晚期肝硬化,这是目前全球尚未满足的需求领域。