背景:我们以前报道过载脂蛋白A2亚型(apoA2-is)作为早期胰腺癌的候选血浆生物标志物。这项研究的目的是apoA2-is的临床开发。
方法:我们根据日本医疗器械质量管理系统的要求,建立了一种新的apoA2-is酶联免疫吸附夹心测定法,并使用2732份血浆样本进行了具有预定终点的体外诊断测试。比较了apoA2-is与CA19-9的临床等效性和意义。
结果:apoA2-ATQ/AT[0.879,95%置信区间(CI):0.832-0.925]用于区分胰腺癌(n=106)和健康对照组(n=106)的曲线下面积的点估计高于CA19-9(0.849,95%CI0.793-0.905),并达到主要终点。基于在2000个健康样本中95%的特异性定义了59.5μg/mL的apoA2-ATQ/AT的截止值,在两个独立的健康队列中,特异性的可靠性分别为95.3%(n=106,95%CI89.4-98.0%)和95.8%(n=400,95%CI93.3-97.3%).apoA2-ATQ/AT检测I期(47.4%)和I/II期(50%)胰腺癌的敏感性均高于CA19-9(36.8%和46.7%,分别)。apoA2-ATQ/AT的组合(截止,59.5μg/mL)和CA19-9(37U/mL)将胰腺癌的敏感性提高到87.7%,而单独的CA19-9则为69.8%。apoA2-is的临床表现被美国国家癌症研究所早期检测研究网络盲目证实。
结论:ApoA2-ATQ/AT作为血液生物标志物的临床表现与CA19-9相当或更好。
We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.
We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9.
The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 μg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 μg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network.
The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.