Novel prognostic biomarkers and their association with survival in pancreatic cancers.

Abstract

296 Background: Early detection of pancreatic cancer would allow for improved survival outcomes. Methods: We retrospectively evaluated serum protease levels and the survival of 15 pancreatic cancer patient samples (6 localized and 9 metastatic) at the KU Cancer Center. Available serum protease assays measured matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), arginase, neutrophil elastase (NE), cathepsin B (CTSB) and cathepsin E (CTSE). The assays utilize fluorescent nanoparticle-based nanobiosensors which increase fluorescence upon posttranslational modification or enzymatic cleavage of targeted compounds and were read by a Spectral scan plate reader. Survival analysis was performed using Kaplan-Meier methods. Results: Baseline characteristics for all 15 patients are in (Table). Median OS was 18.8m in patients with high CTSB expression (mean >51968.9) vs 9.7m in low CTSB expression (p=0.04). Similarly, median OS was 20.4m in high CTSE expression (>123264.8) vs 10m in low CTSE expression (p=0.05). Whereas, median OS was 16.3m in low NE expression (mean <30293.5) vs 9.6m in high NE expression (p=0.06). MMPs, uPA, and Arginase were not associated with survival. Conclusions: Higher CTSB expression is associated with statistically significant improvement in survival. CTSB is a lysosomal protease involved in processing antigens and overexpression could aid in immunologic cancer suppression. CTSB is also involved in the development of desmoplasia which is hypothesized to be a physical barrier to metastasis. CTSE and NE expression did not meet statistically significant association with survival, likely due to sample size. Hence, we identify CTSB as a potential prognostic biomarker in pancreatic cancer. However, these findings need to be validated in a larger study. [Table: see text]