Simultaneous Detection of Zinc and Its Pathway Metabolites Using MALDI MS Imaging of Prostate Tissue

Abstract

Levels of zinc, along with its mechanistically related metabolites citrateand aspartate, are widely reported as reduced in prostate cancer compared to healthytissue and are therefore pointed out as potential cancer biomarkers. Previously, it hasonly been possible to analyze zinc and metabolites by separate detection methods.Through matrix-assisted laser desorption/ionization mass spectrometry imaging (MSI),we were for thefirst time able to demonstrate, in two different sample sets (n= 45 andn= 4), the simultaneous spatial detection of zinc, in the form of ZnCl3−, together withcitrate, aspartate, andN-acetylaspartate on human prostate cancer tissues. The reliabilityof the ZnCl3−detection was validated by total zinc determination using laser ablationinductively coupled plasma MSI on adjacent serial tissue sections. Zinc, citrate, andaspartate were correlated with each other (ranger= 0.46 to 0.74) and showed asignificant reduction in cancer compared to non-cancer epithelium (p< 0.05, log2foldchange range:−0.423 to−0.987), while no significant difference between cancer andstroma tissue was found. Simultaneous spatial detection of zinc and its metabolites is notonly a valuable tool for analyzing the role of zinc in prostate metabolism but might alsoprovide a fast and simple method to detect zinc, citrate, and aspartate levels as abiomarker signature for prostate cancer diagnostics and prognostics.