Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Ann Surg Oncol. 2019 Mar;26(3):807-814. doi: 10.1245/s10434-018-07109-6. Epub 2018 Dec 19.
Thrombospondin-2 (TSP-2) has been reported as an early diagnostic marker for pancreatic ductal adenocarcinoma (PDAC) in Caucasian populations. This study was designed to validateTSP-2 as a diagnostic marker in a large Taiwan cohort and to investigate the association of TSP-2 with the clinical outcomes of PDAC patients.
The serum TSP-2 levels in 263 PDAC patients and 230 high-risk individuals (HRIs) were measured via an enzyme-linked immunosorbent assay. The sensitivity, specificity, and accuracy of TSP-2 as a diagnostic marker to discriminating PDAC patients from HRIs and correlations between TSP-2 levels and prognosis of PDAC patients were analyzed.
Serum TSP-2 levels were significantly higher in patients with PDAC (44.90 ± 40.70 ng/ml) than in the HRIs (17.52 ± 6.23 ng/ml). At a level of ≥ 29.8 ng/ml, TSP-2 exhibited 100% specificity, 55.9% sensitivity, 100% positive predictive value (PPV), and 66.5% negative predictive value (NPV) for discriminating PDAC patients from HRIs. The Cox regression analysis showed that higher serum TSP-2 levels were significantly associated with poor outcomes in PDAC patients (hazard ratio = 1.54, 95% confidence interval = 1.143-2.086, P = 0.005). Combining the carbohydrate antigen 19-9 (CA19-9) (cutoff value of 62.0 U/ml) and TSP-2 (cutoff value of 29.8 ng/ml) levels yielded 98.7% specificity, 90.5% sensitivity, 98.8% PPV, and 90.1% NPV for discriminating patients with PDAC from HRIs.
TSP-2 is a highly specific diagnostic marker and an independent prognostic marker in patients with PDAC. A combined biomarker panel, including TSP-2 and CA19-9, may facilitate future PDAC screening.
在白种人群中，血小板反应蛋白 2（TSP-2）已被报道为胰腺导管腺癌（PDAC）的早期诊断标志物。本研究旨在验证 TSP-2 在台湾大样本队列中的诊断价值，并探讨 TSP-2 与 PDAC 患者临床结局的相关性。
采用酶联免疫吸附试验检测 263 例 PDAC 患者和 230 例高危个体（HRIs）的血清 TSP-2 水平。分析 TSP-2 作为诊断标志物区分 PDAC 患者与 HRIs 的灵敏度、特异性和准确性，以及 TSP-2 水平与 PDAC 患者预后的相关性。
PDAC 患者的血清 TSP-2 水平明显高于 HRIs（44.90±40.70ng/ml 比 17.52±6.23ng/ml）。当水平≥29.8ng/ml 时，TSP-2 对区分 PDAC 患者与 HRIs 的特异性为 100%，灵敏度为 55.9%，阳性预测值（PPV）为 100%，阴性预测值（NPV）为 66.5%。Cox 回归分析显示，较高的血清 TSP-2 水平与 PDAC 患者的不良预后显著相关（风险比=1.54，95%置信区间=1.143-2.086，P=0.005）。联合检测糖抗原 19-9（CA19-9）（截断值 62.0 U/ml）和 TSP-2（截断值 29.8ng/ml）水平，可使区分 PDAC 患者与 HRIs 的特异性达到 98.7%，灵敏度达到 90.5%，PPV 达到 98.8%，NPV 达到 90.1%。
TSP-2 是一种高度特异的诊断标志物，也是 PDAC 患者独立的预后标志物。包括 TSP-2 和 CA19-9 在内的联合生物标志物检测可能有助于未来的 PDAC 筛查。
