甲胎蛋白、甲胎蛋白异质体 3、脱γ-羧基凝血酶原在肝癌检测中的表现：美国的一项 3 期生物标志物研究。
The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC): A Phase 3 Biomarker Study in the United States.
机构信息
Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas; Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Baylor College of Medicine, Houston, Texas.
出版信息
Clin Gastroenterol Hepatol. 2023 Feb;21(2):415-423.e4. doi: 10.1016/j.cgh.2022.01.047. Epub 2022 Feb 3.
BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations.
METHODS
We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12, and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and Hepatocellular Carcinoma Early Detection Screening (HES) scores. We calculated the area under the receiver operating curve and estimated TPR based on an optimal threshold at a fixed FPR of 10%.
RESULTS
The analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6%, 73.8%, and 71.4% for all HCC, and 53.8%, 63.3%, and 61.8 % for early HCC within 6, 12, and 24 months, respectively) but an FPR of 21.5% to 22.9%. However, there were no differences in the area under the receiver operating curve among GALAD, HES, AFP-L3, or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4%, 45.2%, and 46.9%) and was not different from HES (36.4%, 40.5%, and 40.8%) or AFP-L3 alone (39.4%, 45.2%, and 44.9%).
CONCLUSIONS
In a prospective cohort phase III biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false-positive results. GALAD performance was modest and not different from AFP-L3 alone or HES.
背景与目的
甲胎蛋白（AFP）、甲胎蛋白中 Lens culinaris agglutinin 反应性片段（AFP-L3）和去γ-羧基凝血酶原（DCP）联合或在 GALAD（性别、年龄、AFP-L3、AFP 和 DCP）中进行检测，用于回顾性队列和病例对照研究中的肝细胞癌（HCC）监测。然而，北美人群缺乏前瞻性数据和 III 期生物标志物研究。
方法
我们进行了一项前瞻性标本采集、回顾性盲法评估（PRoBE）队列研究，纳入了接受每 6 个月进行肝脏成像和 AFP 监测的肝硬化患者。前瞻性地每 6 个月采集一次血液样本，并以回顾性盲法进行分析。根据单独、联合和 GALAD 以及肝细胞癌早期检测筛查（HES）评分的生物标志物发表阈值，计算 HCC 诊断后 6、12 和 24 个月内任何 HCC 或早期 HCC 的真阳性率（TPR）和假阳性率（FPR）。我们计算了接收者操作特征曲线下的面积，并根据固定 FPR 为 10%时的最佳阈值估计 TPR。
结果
该分析在 534 例患者的队列中进行；50 例患者发生 HCC（68%为早期 HCC），484 例患者的影像学检查结果为阴性。GALAD 的 TPR 最高（所有 HCC 的 TPR 分别为 63.6%、73.8%和 71.4%，早期 HCC 的 TPR 分别为 53.8%、63.3%和 61.8%，在 6、12 和 24 个月内），但 FPR 为 21.5%至 22.9%。然而，在 GALAD、HES、AFP-L3 或 DCP 之间，接收者操作特征曲线下的面积没有差异。在固定的 10%FPR 下，GALAD 的 TPR 下降（6 个月时为 42.4%、12 个月时为 45.2%、24 个月时为 46.9%），与 HES（TPR 分别为 36.4%、40.5%和 40.8%）或 AFP-L3 单独（TPR 分别为 39.4%、45.2%和 44.9%）相比，无显著差异。
结论
在一项前瞻性 III 期生物标志物队列研究中，GALAD 与 HCC 检测的敏感性显著提高有关，但假阳性结果增加。GALAD 的表现一般，与 AFP-L3 单独或 HES 相比无差异。
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