Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen.
Improved diagnosis of pancreatic adenocarcinoma using haptoglobin and serum amyloid A in a panel screen.
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DOI：
10.1007/s00268-008-9853-9
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发表时间：
2009-04
影响因子：
2.6
通讯作者：
Mulvihill, Sean J.
中科院分区：
文献类型：
--
作者：
Firpo, Matthew A.;Gay, David Z.;Granger, Steven R.;Scaife, Courtney L.;DiSario, James A.;Boucher, Kenneth M.;Mulvihill, Sean J.
由于缺乏有效的循环生物标志物，胰腺腺癌（PA）的及时、准确诊断受到阻碍。目前还没有任何一项测试可以改进常用的生物标志物——癌症抗原 19-9 (CA 19-9)，从而有效区分 PA 和良性疾病。本研究的目的是验证两种急性期蛋白（触珠蛋白和血清淀粉样蛋白 A (SAA)）作为 PA 生物标志物，并确定触珠蛋白、SAA 和 CA 19-9 的组合是否会比单独使用 CA 19-9 改善 PA 诊断。通过 ELISA 或比色结合测定法测定了 75 名 PA 患者、32 名慢性胰腺炎患者、42 名其他良性胰腺疾病或胆道狭窄患者以及 150 名健康对照受试者的治疗前血清中触珠蛋白、SAA 和 CA 19-9 的水平。使用方差分析比较各组之间触珠蛋白或 SAA 的相对水平。使用受试者操作特征分析来研究血清触珠蛋白和 SAA 水平的诊断准确性。通过分类树分析，开发了一种在面板诊断筛选中使用触珠蛋白、SAA 和 CA 19-9 的算法。与健康对照受试者 (P < 0.0001) 和慢性胰腺炎患者 (P = 0.01) 相比，PA 患者血清中触珠蛋白和 SAA 均显着升高。与患有其他良性疾病的患者相比，PA 患者血清中的触珠蛋白显着升高（P = 0.0015），而 SAA 在同一比较中没有显着性（P = 0.0508）。受试者操作特征分析表明，在多个阈值截止值上，触珠蛋白 (AUC = 0.792) 是比 SAA (AUC = 0.691) 更好的诊断标志物。使用可最大程度地减少总体错误分类的特定截止值，在区分 PA 病例与所有非 PA 对照时，触珠蛋白的敏感性为 82.7%，特异性为 71.1%，SAA 的敏感性为 34.7%，特异性为 90.2%。在同一样本集中，CA 19-9 的敏感性为 77.3%，特异性为 91.1%。将触珠蛋白、SAA 和 CA 19-9 的数据组合在面板诊断筛选中，比单独使用 CA 19-9 提高了整体准确性，灵敏度为 81.3%，特异性为 95.5%。这些数据表明，当用于组合诊断筛选时，触珠蛋白和 SAA 可用于区分 PA 与良性病症以及健康对照。这项研究支持使用组合生物标志物来提高 PA 诊断的准确性。
Timely and accurate diagnosis of pancreatic adenocarcinoma (PA) is hampered by the lack of effective circulating biomarkers. No single test has emerged that improves upon the commonly used biomarker, cancer antigen 19-9 (CA 19-9) to effectively discriminate PA from benign conditions. The goals of this study were to validate two acute phase proteins, haptoglobin and serum amyloid A (SAA), as biomarkers for PA and determine if the combination of haptoglobin, SAA and CA 19-9 would improve PA diagnosis over CA 19-9 alone. Levels of haptoglobin, SAA and CA 19-9 were measured in pre-treatment sera from 75 PA patients, 32 patients with chronic pancreatitis, 42 patients with other benign pancreatic disease or biliary stricture and 150 healthy control subjects by ELISA or colorimetric binding assay. Relative levels of haptoglobin or SAA were compared between groups using ANOVA. The diagnostic accuracy of serum haptoglobin and SAA levels were investigated using receiver operating characteristics analysis. Using classification tree analysis, an algorithm was developed that used haptoglobin, SAA and CA 19-9 in a panel diagnostic screen. Both haptoglobin and SAA were significantly elevated in sera from PA patients compared to healthy control subjects (P < 0.0001) and patients with chronic pancreatitis (P = 0.01). Haptoglobin was significantly elevated in sera from PA patients relative to patients with other benign diseases (P = 0.0015), whereas SAA fell short of significance in the same comparison (P = 0.0508). Receiver operating characteristic analysis indicated that haptoglobin (AUC = 0.792) was a better diagnostic marker than SAA (AUC = 0.691) over multiple threshold cutoffs. Using specific cutoffs that minimized overall misclassification, haptoglobin yielded a sensitivity of 82.7 % and a specificity of 71.1% and SAA yielded a sensitivity of 34.7% and 90.2% specificity when discriminating PA cases from all non-PA controls. In the same sample set, CA 19-9 yielded a sensitivity of 77.3% and a specificity of 91.1%. Combining data from haptoglobin, SAA and CA 19-9 in a panel diagnostic screen improved overall accuracy over CA 19-9 alone yielding a sensitivity of 81.3% and a specificity of 95.5%. These data demonstrate that haptoglobin and SAA are useful in discriminating PA from benign conditions as well as healthy controls when used in a panel diagnostic screen. This study supports the use of combined biomarkers for improved accuracy in the diagnosis of PA.
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