Analysis and variability of TGFβ measurements in cancer patients with skeletal metastases

Peter J O’Brien1, Rajeev Ramanathan2, Jonathan M Yingling1, Jose Baselga3, Mace L Rothenberg4, Michael Carducci5, Thomas Daly1, Dorothy Adcock2, Michael Lahn11Eli Lilly and Company Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA; 2Esoterix Coagulation, Aurora, CO, USA; 3Vall d’Hebron University Hospital, Barcelona, Spain; 4Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA; 5The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USAAbstract: Transforming growth factor beta (TGFβ) plays an important role in cancer, but accurate measurement of circulating TGFβ is complicated by the high TGFβ content of platelets which can release TGFβ ex vivo. We evaluated the use of citrate-theophylline-adenosine-dipyridamole (CTAD) tubes to reduce preanalytical variation in TGFβ measurements caused by ex vivo platelet activation. CTAD substantially reduced ex vivo platelet activation relative to traditional plasma collections in normal donors, which correlated with a decrease in measured TGFβ levels. We show that TGFβ levels are elevated in the majority of cancer patients with skeletal metastases, and that within-patient variability of these levels is relatively low over several weeks. Patients with elevated TGFβ could be subdivided into groups with or without evidence of platelet contribution to measured TGFβ levels. The use of CTAD tubes allows a better determination of a patient’s TGFβ status, and may improve classification of patients with oncologic disease.Keywords: TGFβ, cancer, biomarker, CTAD