Abstract 2254: A panel of circulating biomarkers in advanced pancreatic cancer
Authors: Hamer Peter J. , Brown-Shimer Sheryl , Ramirez Jessica , Pierce Karen , Bradley Stephen P. , Trivedi Dhaval , Newman Dawn , Carney Walter P. 
Published: February 2011

Background: Pancreatic cancer is one of the deadliest forms of cancer as its five year survival rate is only 4%. There is currently a dearth of circulating biomarkers that have been investigated for pancreatic cancer. We analyzed plasma and serum banks for a variety of circulating biomarkers with potential significance in this cancer or biomarkers known to be targets for new therapeutics in development. Increased PDGFR-B has been seen in pancreatic tumors as compared to normal tissue. Increased TIMP-1 or uPA has been associated with an unfavorable prognosis in many cancers including those of the colon, bladder and breast. Mutations in the K-ras gene occur in a high percentage of pancreatic tumors, therefore we analyzed a subset of samples for circulating Ras p21, as well as for VEGF-165, VEGF-R2 and EphA2.

Methods: 52 EDTA Plasma samples from two pancreatic patient cohorts were analyzed for TIMP-1 and PDGFR-β levels. In addition, 25 pancreatic cancer patient sera were analyzed for TIMP-1, uPA and PDGFR-β. A subset of 20 EDTA plasma samples from one of the cohorts of pancreatic cancer patients were analyzed for circulating Ras p21, VEGF-165, VEGF-R2 and EphA2. The majority of this subset of patients (70%) had stage 3 pancreatic cancer while the remainder had stage 2 or stage 4 disease. ELISA assays used were from Oncogene Science/Siemens Healthcare Diagnostics (Cambridge, MA). Normal ranges and cutoff values were established for each analyte using in-house normal samples. Statistical methods included one-way ANOVA, using Kruskal-Wallis test and Dunn's multiple comparison test.

Results: Data from this study showed that several putative biomarkers were elevated in a large percentage of the advanced pancreatic patients. Of the samples from the plasma cohort, 90% of them were elevated for TIMP-1. Similarly, in the serum cohort, 70% of the samples were elevated for TIMP-1. Of the plasma subset, 45% of the patients had increased EphA2 levels and 60% were increased for VEGF-165 while 77% of the patients had elevated Ras p21 levels.

Conclusions: A high percentage of pancreatic cancer patients have elevated levels of several circulating biomarkers such as Ras p21, VEGF-165, EphA2 and TIMP-1. It is known that a high percentage of pancreatic cancer patients have mutated K-ras genes and the introduction of an assay for circulating ras p21 may assist in deciphering what role Ras p21 plays in pancreatic cancer. In addition, VEGF-165 is the target of many current and future anti-angiogenesis drugs. A panel of markers such as those analyzed in this study of pancreatic cancer has the potential for use as a selection tool for targeted therapies such as EphA2 targeted therapies under development. In addition, biomarker panels, which may include traditional tumor markers, may have utility in monitoring patient therapy.

1

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2254.