Platelet proteins clusterin, cofilin-1 and glutathione synthetase as biomarker for early detection of colorectal cancer

Abstract

Introduction: Colorectal cancer (CRC) is one of the most frequent malignancies in the western world. Early tumor detection and intervention are important determinants on CRC patient survival. During tumor proliferation, platelets store and segregate proteins, which therefore could potentially serve as screening markers for early malignancy. Material and Methods: Protein profiles of platelets between healthy volunteers (n = 12) and patients with early- (n = 7) and late-stage (n = 5) CRCs were compared using multiplex-fluorescence two-dimensional gel electrophoresis. Differences in protein levels between these groups were analyzed with SameSpots® software followed by Principle Component Analysis. Proteins of interest were identified by mass spectrometry. Target proteins were validated by multiplex-fluorescence-based Western blot analyses using an independent cohort of platelet protein samples [healthy controls (n = 15), early CRCs (n = 15), late CRCs (n = 15)]. Results: By inter-group comparison, 39 differentially expressed protein spots were detected (p < 0.05) between healthy controls and patients with early- and late-stage CRCs. Of those, Clusterin was lower expressed especially in early-stage CRCs, whereas Cofilin-1 and Glutathione synthetase (GSH-S) were present at higher levels in platelets from early-stage CRC patients compared to control individuals. These expression characteristics were confirmed by Western blot analyses in an independent cohort. Conclusion: Different protein levels within platelets distinguishing healthy controls from patients with early- and late-stage CRCs were identified. The potential of Clusterin, Cofilin-1 and GSH-S as platelet biomarkers, in particular for early detection of CRC, should be confirmed in a prospective multicenter trial.