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血小板反应蛋白-2 是一种高度特异性的诊断标志物,与胰腺癌的预后相关。

Thrombospondin-2 is a Highly Specific Diagnostic Marker and is Associated with Prognosis in Pancreatic Cancer.

机构信息

Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Ann Surg Oncol. 2019 Mar;26(3):807-814. doi: 10.1245/s10434-018-07109-6. Epub 2018 Dec 19.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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%。

结论

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。

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