Implementation of MALDI Mass Spectrometry Imaging in Cancer Proteomics Research: Applications and Challenges

Berghmans, Eline; Boonen, Kurt; Maes, Evelyne; Mertens, Inge; Pauwels, Patrick; Baggerman, Geert

doi:10.3390/jpm10020054

Cited by 21 publications

(17 citation statements)

References 43 publications

(80 reference statements)

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“…All these feature makes MALDI the ideal technique for routine clinical analysis, as demonstrated by the huge number of existing applications for diagnostic purposes [ 19 , 20 , 21 ]. MALDI has indeed demonstrated a great potential when applied to the fight against cancer [ 22 ], and part of the huge amount of work performed on tumor-related topics, including the analysis of drugs [ 23 ], MALDI-imaging developments [ 24 , 25 ], diagnosis of ovarian [ 26 ], non-small cell lung [ 27 ], and prostate [ 28 ] cancer, has very recently been reviewed.…”

Section: Introductionmentioning

confidence: 99%

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

Zambonin

Aresta

2022

Molecules

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Cancer represents a group of heterogeneous diseases that are a leading global cause of death. Even though mortality has decreased in the past thirty years for different reasons, most patients are still diagnosed at the advanced stage, with limited therapeutic choices and poor outcomes. Moreover, the majority of cancers are detected using invasive painful methods, such as endoscopic biopsy, making the development of non-invasive or minimally invasive methods for the discovery and fast detection of specific biomarkers a crucial need. Among body fluids, a valuable non-invasive alternative to tissue biopsy, the most accessible and least invasive are undoubtedly urine and saliva. They are easily retrievable complex fluids containing a large variety of endogenous compounds that may provide information on the physiological condition of the body. The combined analysis of these fluids with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS), a reliable and easy-to-use instrumentation that provides information with relatively simple sample pretreatments, could represent the ideal option to rapidly achieve fast early stage diagnosis of tumors and their real-time monitoring. On this basis, the present review summarizes the recently reported applications relevant to the MALDI analysis of human urine and saliva samples.

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Section: Introductionmentioning

confidence: 99%

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

Zambonin

Aresta

2022

Molecules

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“…Molecular histology impacts many aspects of histopathological diagnostics and research and thus MSI is emerging as a powerful technology in translational studies [ 1 , 2 ]. In particular, the analysis of tumor tissues with pronounced cellular and morphological heterogeneity benefits from the spatially resolved MSI technology [ 3 , 4 ]. Common applications for MSI in cancer studies include tumor typing and subtyping [ 5 – 7 ], studying resection margins and tumor heterogeneity [ 8 , 9 ], and finding biomarkers for tumor diagnosis, prognosis or prediction [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: a case study of an urothelial cancer cohort analyzed in the Galaxy framework

et al. 2022

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Background Mass spectrometry imaging (MSI) derives spatial molecular distribution maps directly from clinical tissue specimens and thus bears great potential for assisting pathologists with diagnostic decisions or personalized treatments. Unfortunately, progress in translational MSI is often hindered by insufficient quality control and lack of reproducible data analysis. Raw data and analysis scripts are rarely publicly shared. Here, we demonstrate the application of the Galaxy MSI tool set for the reproducible analysis of a urothelial carcinoma dataset. Methods Tryptic peptides were imaged in a cohort of 39 formalin-fixed, paraffin-embedded human urothelial cancer tissue cores with a MALDI-TOF/TOF device. The complete data analysis was performed in a fully transparent and reproducible manner on the European Galaxy Server. Annotations of tumor and stroma were performed by a pathologist and transferred to the MSI data to allow for supervised classifications of tumor vs. stroma tissue areas as well as for muscle-infiltrating and non-muscle infiltrating urothelial carcinomas. For putative peptide identifications, m/z features were matched to the MSiMass list. Results Rigorous quality control in combination with careful pre-processing enabled reduction of m/z shifts and intensity batch effects. High classification accuracy was found for both, tumor vs. stroma and muscle-infiltrating vs. non-muscle infiltrating urothelial tumors. Some of the most discriminative m/z features for each condition could be assigned a putative identity: stromal tissue was characterized by collagen peptides and tumor tissue by histone peptides. Immunohistochemistry confirmed an increased histone H2A abundance in the tumor compared to the stroma tissues. The muscle-infiltration status was distinguished via MSI by peptides from intermediate filaments such as cytokeratin 7 in non-muscle infiltrating carcinomas and vimentin in muscle-infiltrating urothelial carcinomas, which was confirmed by immunohistochemistry. To make the study fully reproducible and to advocate the criteria of FAIR (findability, accessibility, interoperability, and reusability) research data, we share the raw data, spectra annotations as well as all Galaxy histories and workflows. Data are available via ProteomeXchange with identifier PXD026459 and Galaxy results via https://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links. Conclusion Here, we show that translational MSI data analysis in a fully transparent and reproducible manner is possible and we would like to encourage the community to join our efforts.

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“…The thousands of generated mass spectra can be combined. This thus provides not only structural information about the AMP, it also retains its spatial distribution and information on the relative abundance throughout the tissue [27]. This can overcome the limitation of antibody-related visualization with AMP-specific antibodies that are in some cases designed towards the non-active part of the AMP.…”

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry (Imaging) for Detection and Identification of Cyclic AMPs: Focus on Human Neutrophil Peptides (HNPs)

Berghmans¹,

Baggerman²

2022

Insights on Antimicrobial Peptides

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Antimicrobial peptides (AMPs) are known best for their role in innate immunity against bacteria, viruses, parasites and fungi. However, not only are they showing increasing promise as potential antimicrobial drug candidates, recently, it has been reported that certain AMPs also show a cytotoxic effect against cancer cells. Their possible antitumor effect could make AMPs interesting candidate cancer biomarkers and a possible lead for new anticancer therapy. Due to their cyclic structure, detection and identification of AMPs is challenging, however, mass spectrometry (imaging; MSI) has been shown as a powerful tool for visualization and identification of (unknown) cyclic AMPs. In this chapter, we will discuss how mass spectrometry (imaging), combined with the use of electron-transfer dissociation (ETD) as fragmentation technique, can be used as a reliable method to identify AMPs in their native cyclic state. Using this approach, we have previously detected and identified human neutrophil peptides (HNPs) as important AMPs in cancer, of which a detailed bacterial, viral and cancer-related overview will be presented.

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Implementation of MALDI Mass Spectrometry Imaging in Cancer Proteomics Research: Applications and Challenges

Cited by 21 publications

References 43 publications

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: a case study of an urothelial cancer cohort analyzed in the Galaxy framework

Mass Spectrometry (Imaging) for Detection and Identification of Cyclic AMPs: Focus on Human Neutrophil Peptides (HNPs)

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