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

2020 ◽  
Vol 10 (2) ◽  
pp. 54
Author(s):  
Eline Berghmans ◽  
Kurt Boonen ◽  
Evelyne Maes ◽  
Inge Mertens ◽  
Patrick Pauwels ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cancer Research ◽  
Drug Targets ◽  
Mass Spectrometry Imaging ◽  
Tumor Biology ◽  
Differential Forms ◽  
Maldi Mass Spectrometry ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Effective Diagnosis

Studying the proteome–the entire set of proteins in cells, tissues, organs and body fluids—is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may lead to a better understanding of tumor biology and to a more effective diagnosis, prognosis, recurrence and response to therapy. Moreover, proteins can act as a biomarker or potential drug targets. Hence, it is of major importance to implement proteomic, particularly mass spectrometric, approaches in cancer research, to provide new crucial insights into tumor biology. Recently, mass spectrometry imaging (MSI) approaches were implemented in cancer research, to provide individual molecular characteristics of each individual tumor while retaining molecular spatial distribution, essential in the context of personalized disease management and medicine.

A novel proteomic mass spectrometry-based approach to reveal functionally heterogeneous tumor clones in breast cancer metastases and identify clone-specific drug targets.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13063-e13063
Author(s):  
Nawale Hajjaji ◽  
Mira Abbouchi ◽  
Lan Anh Nguyen ◽  
Samuel Charles ◽  
Sarah Leclercq ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Drug Targets ◽  
Tumor Heterogeneity ◽  
Mass Spectrometry Imaging ◽  
Maldi Mass Spectrometry ◽  
Breast Cancer Metastases ◽  
Spatially Resolved ◽  
Cancer Metastases ◽  
Candidate Drug

e13063 Background: Breast cancer mortality is expected to rise by almost 30% by 2030 worldwide, mainly due to the occurrence of distant metastases. The development of drugs specifically targeted at tumor drivers has not yet curbed resistance to treatment, which prevents metastases curability. There is a need for new molecular approaches to tackle metastases complex biology, particularly tumor heterogeneity, a main determinant of resistance. The aim of this study was to use a proteomic mass spectrometry-based approach to reveal functionally heterogeneous’ tumor subpopulations in breast cancer metastases, and identify clone specific drug targets. Methods: Metastasis biopsies (n = 21) were collected retrospectively from patients with advanced breast cancer treated at Oscar Lambret Cancer Center (Lille, France). Tumor heterogeneity was analyzed directly on FFPE tissue sections using MALDI mass spectrometry imaging (MSI) on a RapifleX Tissuetyper. Unsupervised spatial segmentation was performed to reveal tumor subpopulations with distinct proteomic profiles within each metastasis. The full proteomic characterization of these tumor clones was further performed with spatially resolved proteomic mass spectrometry. Results: MSI revealed that breast cancer metastases contained 2 to 5 functionally distinct tumor clones (proteomic clones). Although the clone profiles within a metastasis were correlated, unsupervised hierarchical clustering showed a clear distinction between them and specific proteomic signatures. Enrichment analysis showed that differentially expressed proteins were involved in a variety of biological processes or pathways including regulation of histone acetylation, extracellular matrix degradation, DNA repair, NOTCH pathway, estrogen-responsive target genes or exocytosis. The evolution of the proteomic clones profile during disease progression was also determined by comparison of paired biopsies. To identify the candidate treatments best fitted to metastasis heterogeneity, the specific proteomic signatures of the clones were matched against a druggable genome database. It was possible to unveil candidate drug targets personalized to each metastasis functional clone. Conclusions: MALDI mass spectrometry imaging combined with spatially resolved proteomics has the potential to tackle breast cancer metastases heterogeneity, and identify candidate drug targets specific to functional clones to personalize treatments.

scholarly journals Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study

2021 ◽  
Author(s):  
Riccardo Zecchi ◽  
Pietro Franceschi ◽  
Laura Tigli ◽  
Davide Amidani ◽  
Chiara Catozzi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sample Preparation ◽  
Mass Spectrometry Imaging ◽  
Maldi Mass Spectrometry ◽  
Adult Rabbit ◽  
Chronic Obstructive ◽  
Ionization Mass ◽  
Obstructive Pulmonary Disease ◽  
Imaging Protocol ◽  
Girard’S Reagent

AbstractCorticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard’s reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples. Graphical abstract

Matrix Sublimation Device for MALDI Mass Spectrometry Imaging

2018 ◽  
Vol 91 (1) ◽  
pp. 803-807 ◽  
Author(s):  
Roberto Fernández ◽  
Jone Garate ◽  
Lucia Martín-Saiz ◽  
Igor Galetich ◽  
José A. Fernández
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Maldi Mass Spectrometry ◽  
Maldi Mass Spectrometry Imaging

scholarly journals Mass Spectrometry Imaging Using Dynamically Harmonized FT-ICR at Million Resolving Power: Rationalizing and Optimizing Sample Preparation and Instrumental Parameters

2020 ◽  
Author(s):  
Mathieu Tiquet ◽  
Raphaël La Rocca ◽  
Daan van Kruining ◽  
Pilar Martinez-Martinez ◽  
Gauthier Eppe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Mass Spectrometry Imaging ◽  
Mass Range ◽  
Maldi Mass Spectrometry ◽  
Mass Accuracy ◽  
Ion Current ◽  
Resolving Power ◽  
Lipid Mass ◽  
The Stability

<p><i>MALDI mass spectrometry imaging (MSI) is a powerful analytical method giving access to the 2D localizations of compounds in a thin section of a sample. To properly discern isobaric compounds in complex biological samples, dynamically harmonized ICR cell (ParaCell©) has been introduce to achieve extreme spectral resolution. However, high resolution MS images realized on a 9.4T FTICR High resolution instrument with recommended parameters suffered from an abnormal shifting of m/z ratios pixel to pixel. Resulting datasets show poor mass accuracy measurements and resolutions under estimations. By following the behavior of the Total Ion Current in function of the number of laser shots, the abnormal mass shifting phenomenon has been linked to the stability of the Total Ion Current (TIC) during images acquisitions. An optimization of laser parameters is proposed in order to limit the observed mass shift to retain machine specifications during MSI analyses. It is also shown that the method has been successfully employed to realize quality MS images with resolution above 1,000,000 in the lipid mass range across the whole image.</i></p>

Sign in / Sign up

Export Citation Format

Share Document