Clinical laboratory testing for HER2 status in breast cancer tissues is critically important for therapeutic decision making. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating proteins through the direct and morphology-driven analysis of tissue sections. We hypothesized that MALDI-IMS may determine HER2 status directly from breast cancer tissues. Breast cancer tissues (n = 48) predefined for HER2 status were subjected to MALDI-IMS, and protein profiles were obtained through direct analysis of tissue sections. Protein identification was performed by tissue microextraction and fractionation followed by top-down tandem mass spectrometry. A discovery and an independent validation set were used to predict HER2 status by applying proteomic classification algorithms. We found that specific protein/peptide expression changes strongly correlated with the HER2 overexpression. Among these, we identified m/z 8404 as cysteine-rich intestinal protein 1. The proteomic signature was able to accurately define HER2-positive from HER2-negative tissues, achieving high values for sensitivity of 83%, for specificity of 92%, and an overall accuracy of 89%. Our results underscore the potential of MALDI-IMS proteomic algorithms for morphology-driven tissue diagnostics such as HER2 testing and show that MALDI-IMS can reveal biologically significant molecular details from tissues which are not limited to traditional high-abundance proteins.
We have probed for reaction intermediates involved in the dual-gold-catalyzed activation of a conjugated 1,5-diyne substrate and its further coupling to benzene in the liquid phase. This was done by sampling the reaction mixture by electrospray ionization followed by high-resolution ion mobility mass spectrometryunder conditions allowing for the resolution of structural isomers differing in their collision cross sections by less than 0.5%. For the cationic mass corresponding to catalyst + diyne (activation stage) we resolve four isomers. At the mass corresponding to catalyst + diyne + benzene, two isomers are observed. By comparing the experimentally obtained cross sections to those inferred for model structures derived from density functional computations, we find our measurements to be consistent with the proposed solution mechanism. This constitutes the first direct observation of intermediates in dual gold catalysis and supports the previous inference that the mechanism involves cooperative interactions between two gold centers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.