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Open Access Research

Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis

Stephanie T Chang1, Jacob M Zahn23, Joe Horecka23, Pamela L Kunz5, James M Ford45, George A Fisher5, Quynh T Le1, Daniel T Chang1, Hanlee Ji25 and Albert C Koong1*

Author Affiliations

1 Department of Radiation Oncology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA

2 Stanford Genome Technology Center, Stanford University School of Medicine, Stanford University, Stanford, CA, USA

3 Department of Biochemistry, Stanford University School of Medicine, Stanford University, Stanford, CA, USA

4 Department of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA

5 Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA

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Journal of Translational Medicine 2009, 7:105  doi:10.1186/1479-5876-7-105

Published: 11 December 2009

Abstract

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.