采用多重邻近连接检测分析鉴定生物标志物谱可提高胰腺癌诊断的准确性。
Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis.
机构信息
Department of Radiation Oncology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
出版信息
J Transl Med. 2009 Dec 11;7:105. doi: 10.1186/1479-5876-7-105.
BACKGROUND
Pancreatic cancer continues to prove difficult to clinically diagnose. Multiple simultaneous measurements of plasma biomarkers can increase sensitivity and selectivity of diagnosis. Proximity ligation assay (PLA) is a highly sensitive technique for multiplex detection of biomarkers in plasma with little or no interfering background signal.
METHODS
We examined the plasma levels of 21 biomarkers in a clinically defined cohort of 52 locally advanced (Stage II/III) pancreatic ductal adenocarcinoma cases and 43 age-matched controls using a multiplex proximity ligation assay. The optimal biomarker panel for diagnosis was computed using a combination of the PAM algorithm and logistic regression modeling. Biomarkers that were significantly prognostic for survival in combination were determined using univariate and multivariate Cox survival models.
RESULTS
Three markers, CA19-9, OPN and CHI3L1, measured in multiplex were found to have superior sensitivity for pancreatic cancer vs. CA19-9 alone (93% vs. 80%). In addition, we identified two markers, CEA and CA125, that when measured simultaneously have prognostic significance for survival for this clinical stage of pancreatic cancer (p < 0.003).
CONCLUSIONS
A multiplex panel assaying CA19-9, OPN and CHI3L1 in plasma improves accuracy of pancreatic cancer diagnosis. A panel assaying CEA and CA125 in plasma can predict survival for this clinical cohort of pancreatic cancer patients.
背景
胰腺癌的临床诊断仍然颇具难度。对多种血浆生物标志物进行同步测量可以提高诊断的灵敏度和特异性。临近连接分析（PLA）是一种高度灵敏的技术，可用于对血浆中的生物标志物进行多重检测，几乎没有或没有背景信号干扰。
方法
我们使用多重临近连接分析检测了 52 例局部晚期（Ⅱ/Ⅲ期）胰腺导管腺癌病例和 43 名年龄匹配的对照者的血浆中 21 种生物标志物的水平。使用 PAM 算法和逻辑回归建模的组合计算了用于诊断的最佳生物标志物组合。使用单变量和多变量 Cox 生存模型确定了在组合中具有显著预后意义的生物标志物。
结果
与单独检测 CA19-9 相比，在多重检测中测量的三种标志物（CA19-9、OPN 和 CHI3L1）对胰腺癌具有更高的灵敏度（93%对 80%）。此外，我们发现了两种标志物，CEA 和 CA125，当同时测量时，对该临床阶段胰腺癌的生存具有预后意义（p < 0.003）。
结论
在血浆中同时检测 CA19-9、OPN 和 CHI3L1 的多重检测可以提高胰腺癌诊断的准确性。在血浆中同时检测 CEA 和 CA125 的检测可以预测该临床队列胰腺癌患者的生存情况。
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