Derivatization-Mediated MALDI-MSI and CE-LIF for Collaborative Analysis of Monosaccharides in Endometrial Cancer Patients: From Pathological Tissues to Serum

Abnormal glucose metabolism has been identified as a key characteristic of tumorigenesis. Visualizing the levels of monosaccharides in the lesion tissues and bodies of cancer patients is conducive to uncovering patterns of glucose metabolic reprogramming and assisting in the early diagnosis of cancer. Consequently, based on 7-(diethylamino)coumarin-3-carbohydrazide (DCCH), which has mass spectrometry/optical dual-signal enhancement functionality, both an on-tissue derivatization strategy suitable for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) analysis and an in-solution derivatization strategy for capillary electrophoresis/laser-induced fluorescence (CE-LIF) analysis have been developed. During the on-tissue derivatization reaction, the nonvolatile MALDI matrix, 2,5-dihydroxybenzoic acid, was innovatively adopted as a proton donor. This approach not only efficiently catalyzes the derivatization process but also significantly minimizes analyte redistribution, and a low-cost airbrush application can achieve satisfying in situ derivatization. For further addressing the issue of the coexistence of multiple conformational isomers in biosamples, a rapid and efficient CE-LIF method was proposed for the separation of five DCCH-labeled monosaccharides (including three conformational isomers) within 8 min. By focusing on endometrial cancer (EC), the synergy of DCCH-mediated MALDI-MSI and CE-LIF analysis successfully achieved high-resolution in situ visualization of an obvious depletion difference in monosaccharides across the focal areas (tumor tissues, peritumoral tissues, and paracancerous tissues), and a comparative analysis was conducted on the serum monosaccharide profiles between patients with EC and those with benign uterine diseases. These analyses yielded novel molecular-level evidence, thereby facilitating a deeper understanding of the monosaccharide metabolic abnormalities associated with EC.