Assessment of Serum Platelet Factor 4 as a Predictive Marker for VTE and as a Prognostic Biomarker in Pancreatic, Colorectal, Breast, and Lung Cancer

Abstract

Introduction: Cancer is the second leading cause of mortality in the United States, with lung, colorectal, breast, and pancreas carcinoma comprising the four leading causes of cancer death. We previously demonstrated that platelet factor 4 (PF4) is an independent prognostic factor in pancreatic adenocarcinoma, with a significant association between elevated serum levels and increased venous thromboembolism (VTE) incidence and death. It is possible that high serum PF4 levels may be a useful biomarker for patient stratification for directing VTE prophylaxis in cancer patients. We sought to determine if PF4 is useful as a biomarker for prognosis and VTE incidence in other common cancers. Methods: We measured PF4 levels in sera from 39 patients with breast cancer, 48 with colorectal cancer, 50 with lung cancer and compared these results with data from 132 patients with pancreatic adenocarcinoma using a commercially available ELISA kit. Results: for all four cancers, age (P < 0.0001) and stage (P < 0.0001) were both significant predictors of survival. When examined in univariate Cox models, serum PF4 was a significant predictor of survival in breast (P = 0.018), colorectal (P = 0.01), and pancreatic (P = 0.003) cancer but not lung cancer (P = 0.65). After correcting for age and stage in multivariate analyses, PF4 remained a significant prognostic indicator in only colorectal (P = 0.008) and pancreatic (P = 0.001) cancers, with resulting hazard ratios for mortality of 1.53 and 1.105 respectively. Serum PF4 levels were significantly elevated in colorectal (P = 0.04) and pancreatic (P = 0.008) cancer subjects with VTE as compared to those without VTE, but this relationship was not present in breast (P = 0.81) or lung (P = 0.29) cancer subjects. When adjusted for age and stage, this association between serum PF4 level and VTE remained significant only in pancreatic cancer (P = 0.015). Conclusions: These initial results suggest PF4 may have utility as a clinical biomarker to predict survival in patients with pancreatic, and colorectal cancer and may be useful for patient stratification for VTE prophylaxis. We hypothesize that colon and pancreatic cancer patients with high serum PF4 levels may benefit from extended VTE prophylaxis. This question should be answered in a clinical trial.