A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3 PLOS ONE Shultz, D. B., Pai, J., Chiu, W., Ng, K., Hellendag, M. G., Heestand, G., Chang, D. T., Tu, D., Moore, M. J., Parulekar, W. R., Koong, A. C. 2016; 11 (1)

Abstract

NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS) in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples.Using the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker.Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251) and validation sets (229). Among all patients, elevated levels of interleukin-8 (IL-8), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1-alpha (HIF-1 alpha), and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2) expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention.ClinicalTrials.gov NCT00040183.

View details for DOI 10.1371/journal.pone.0147995

View details for Web of Science ID 000369527800261

View details for PubMedID 26808546