Prospective on Imaging Mass Spectrometry in Clinical Diagnostics

Moore, Jessica L.; Patterson, Nathan Heath; Norris, Jeremy L.; Caprioli, Richard M.

doi:10.1016/j.mcpro.2023.100576

Cited by 18 publications

(10 citation statements)

References 86 publications

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“…As a non-targeted approach for defining alterations in tissues exhibiting atrophic gastritis, we used matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS) ( 53 , 54 ). IMS provides insight into the spatial distribution and relative abundance of molecules, including lipids, peptides, and proteins; in this case, gastric peptides were analyzed.…”

Section: Resultsmentioning

confidence: 99%

Remodeling of the gastric environment in Helicobacter pylori -induced atrophic gastritis

Shuman,

Lin,

Westland

et al. 2024

mSystems

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Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori -induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori -infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry. We detected striking differences in the protein content of corpus and antrum tissues. Four hundred ninety-two proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori -infected corpus tissues exhibiting atrophic gastritis compared with infected corpus tissues exhibiting non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. The corresponding alterations were not detected in animals infected with a H. pylori ∆ cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions. IMPORTANCE A normal stomach is organized into distinct regions known as the corpus and antrum, which have different functions, cell types, and gland architectures. Previous studies have primarily used histologic methods to differentiate these regions and detect H. pylori -induced alterations leading to stomach cancer. In this study, we investigated H. pylori -induced gastric molecular alterations in a Mongolian gerbil model of carcinogenesis. We report the detection of numerous proteins that are preferentially localized to the gastric corpus but not the antrum in a normal stomach. We show that stomachs with H. pylori- induced atrophic gastritis (a precancerous condition characterized by the loss of specialized cell types) exhibit marked changes in the abundance and localization of proteins normally localized to the gastric corpus. These results provide new insights into H. pylori -induced gastric molecular alterations that are associated with the development of stomach cancer.

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Section: Resultsmentioning

confidence: 99%

Remodeling of the gastric environment in Helicobacter pylori -induced atrophic gastritis

Shuman,

Lin,

Westland

et al. 2024

mSystems

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“…Tissue volumes were estimated using commercially available biopsy punches based on needs (0.35 mm, 0.5 mm, 0.75 mm, 1 mm, 1.5 mm, 2 mm, 3 mm; Integra Miltex, the United States). Specifically, the formula to calculate the volume is: volume (nL) = π × (D/2F) 2 × h × 10 - 6 , where D is the diameter (µm) of the punch, F is the expansion factor calculated as the square root of the ratio of the tissue area after expansion to the area before expansion, and h is the thickness (µm) of the slice. The detection range calibration curves were estimated using Local Polynomial Regression Fitting estimation (loess) using the number of identified peptides and proteins.…”

Section: Methodsmentioning

confidence: 99%

Filter-aided expansion proteomics

Dong,

Zhu,

Zhang

et al. 2023

Preprint

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Integration of hydrogel-based tissue expansion and mass spectrometry-based proteomics enables high spatial resolution analysis of global protein expression in tissues. Here, we introduce a filter-aided tissue expansion proteomics (FAXP) method with optimized hydrogel preparation and treatment steps for spatial proteomics analysis of formalin-fixed paraffin-embedded (FFPE) specimens. Compared with our original ProteomEx method, FAXP, partially automated with robotics, exhibited 14.5-fold higher volumetric resolution, increased peptide yield leading to 250% more protein identifications, and 50% time consumption for sample preparation. We demonstrated its application in clinical colorectal tissue samples. We further integrated it with laser capture microdissection for proteomic analysis of subcellular organelles.

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“…The rapid developments of novel proteomic technologies and applications has led to the establishment of many specialized approaches focusing on targeted biomarker proteomics [63,64], clinical proteomics [65,66], drug discovery and pharmaco-proteomics [67][68][69], proteogenomics [70,71], membrane proteomics [72,73], extracellular matrix proteomics [74,75], native proteomics [76][77][78], thermal proteome profiling [79], the analysis of protein conformations and interactions via chemical cross-linking MS [80,81] and subcellular/organelle proteomics [82,83]. The more recently developed discipline of native MS focuses on the detailed top-down characterization of structural heterogeneity in protein isoforms under non-denaturing conditions, making this approach an important part of structural cell biology [84,85].…”

Section: The Importance Of Proteomics and The Concept Of Proteoforms ...mentioning

confidence: 99%

Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology

Dowling,

Swandulla,

Ohlendieck

2023

Cells

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Voluntary striated muscles are characterized by a highly complex and dynamic proteome that efficiently adapts to changed physiological demands or alters considerably during pathophysiological dysfunction. The skeletal muscle proteome has been extensively studied in relation to myogenesis, fiber type specification, muscle transitions, the effects of physical exercise, disuse atrophy, neuromuscular disorders, muscle co-morbidities and sarcopenia of old age. Since muscle tissue accounts for approximately 40% of body mass in humans, alterations in the skeletal muscle proteome have considerable influence on whole-body physiology. This review outlines the main bioanalytical avenues taken in the proteomic characterization of skeletal muscle tissues, including top-down proteomics focusing on the characterization of intact proteoforms and their post-translational modifications, bottom-up proteomics, which is a peptide-centric method concerned with the large-scale detection of proteins in complex mixtures, and subproteomics that examines the protein composition of distinct subcellular fractions. Mass spectrometric studies over the last two decades have decisively improved our general cell biological understanding of protein diversity and the heterogeneous composition of individual myofibers in skeletal muscles. This detailed proteomic knowledge can now be integrated with findings from other omics-type methodologies to establish a systems biological view of skeletal muscle function.

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Prospective on Imaging Mass Spectrometry in Clinical Diagnostics

Cited by 18 publications

References 86 publications

Remodeling of the gastric environment in Helicobacter pylori -induced atrophic gastritis

Remodeling of the gastric environment in Helicobacter pylori -induced atrophic gastritis

Filter-aided expansion proteomics

Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology

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