Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma

Han, Eric C.; Lee, Ying Shiung; Liao, Wenlin; Liu, Yu Ching; Liao, Hsin Yi; Jeng, Long Bin

doi:10.1016/j.cca.2010.09.021

Cited by 26 publications

(21 citation statements)

References 34 publications

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“…Each ion within the spectrum can then be viewed for its spatial distribution and relative intensity across the entire section. Molecular correlations with spatial distinctions can be clearly observed and compared in normal and diseased tissues (5,6).…”

Section: Protein Analysismentioning

confidence: 99%

Imaging of Intact Tissue Sections: Moving beyond the Microscope

Seeley¹,

Schwamborn²,

Caprioli

2011

Journal of Biological Chemistry

106

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MALDI-imaging MS is a new molecular imaging technologyfor direct in situ analysis of thin tissue sections. Multiple analytes can be monitored simultaneously without prior knowledge of their identities and without the need for target-specific reagents such as antibodies. Imaging MS provides important insights into biological processes because the native distributions of molecules are minimally disturbed, and histological features remain intact throughout the analysis. A wide variety of molecules can be imaged, including proteins, peptides, lipids, drugs, and metabolites. Several specific examples are presented to highlight the utility of the technology. MALDI imaging MS (IMS)4 is an emerging new tool for the analysis of biological and clinical tissue samples. It has been shown to be amenable for the analysis of proteins, peptides (both endogenous and enzymatically produced), lipids, and small molecules (such as drugs and endogenous metabolites). Spatial relationships of molecules within a specimen are preserved because intact tissue is directly analyzed without homogenization. In this way, molecules can be interrogated in their native environments, providing new insights into the biological processes involved.IMS requires minimal sample preparation for analysis. Thin sections of tissue samples (typically, 5-10 m thick) are obtained from frozen or formalin-fixed paraffin-embedded (FFPE) tissue blocks and collected on conductive MALDI targets. A matrix compound (typically, a small organic acid as well as a proteolytic enzyme when necessary) is applied to the surface of the tissue sample. Mass spectra are subsequently collected by firing a laser in an ordered pattern of thousands of ablated spots on the tissue section, and a discrete spectrum is collected from each location on the sample. Each ablated spot is analogous to a pixel in a digital photograph. Each pixel (spectrum) contains many analytes that can be individually displayed as a function of their position and relative intensity within the tissue section. In this way, hundreds of images from specific molecular species can be generated simultaneously from a single tissue section without prior knowledge of their identities. Specific reagents such as antibodies are not needed. Alternatively, IMS can be carried out in a profiling mode in which only relatively small selected areas from each tissue section are targeted for analysis. A stained serial section is typically used to guide the analysis. The sample preparation and analysis process of fresh-frozen and FFPE tissues are summarized in Fig. 1.IMS can be very high-throughput in nature. Often, 10 -20 tissue sections can be collected on a single target plate and analyzed concurrently. With currently available high repetition rate lasers (1 kHz or greater), the entire target plate can be analyzed in a matter of a few minutes to a few hours, depending on the desired spatial resolution. It has recently been shown that, through the use of a 5 kHz laser and continuous laser raster, a rat brain measuring 185 mm 2 can ...

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Section: Protein Analysismentioning

confidence: 99%

Imaging of Intact Tissue Sections: Moving beyond the Microscope

Seeley¹,

Schwamborn²,

Caprioli

2011

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

show abstract

“…This opens the way for specific and cancer-related in situ biomarker analysis and identification. In a histology-driven way, other groups have employed MALDI-IMS to study the proteome of renal cell carcinoma tumor margins (Oppenheimer et al 2010), hepatocellular carcinoma and corresponding non-tumor junction sections (Han et al 2011), and ovarian cancer interface zones (Kang et al 2010).…”

Section: Maldi-ims For Investigation Of Tumor Biologymentioning

confidence: 99%

MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications

Balluff

Schöne

Höfler

et al. 2011

Histochem Cell Biol

111

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Matrix assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a method that allows the investigation of the molecular content of tissues within its morphological context. Since it is able to measure the distribution of hundreds of analytes at once, while being label free, this method has great potential which has been increasingly recognized in the field of tissue-based research. In the last few years, MALDI-IMS has been successfully used for the molecular assessment of tissue samples mainly in biomedical research and also in other scientific fields. The present article will give an update on the application of MALDI-IMS in clinical and preclinical research. It will also give an overview of the multitude of technical advancements of this method in recent years. This includes developments in instrumentation, sample preparation, computational data analysis and protein identification. It will also highlight a number of emerging fields for application of MALDI-IMS like drug imaging where MALDI-IMS is used for studying the spatial distribution of drugs in tissues.

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“…This technology allows for the visualization of the distribution of biomolecules (peptides, proteins and lipids) across a tissue section where the relative abundance of hundreds of biomolecules can be mapped across the entire tissue section [8][9][10][11][12][13]. It is thus possible to use MALDI-IMS spectral data of tissue biopsies to detect numerous cancer-associated biochemical changes [14].…”

Section: Introductionmentioning

confidence: 99%

Assessment of molecular differentiation in FFPE colon adenocarcinoma tissues using PCA analysis of MALDI IMS spectral data

Panderi¹,

Perez²,

Cao³

et al. 2017

J Appl Bioanal

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MALDI IMS datasets comprise huge amounts of spectra and their interpretation requires the use of multivariate statistical methods. MALDI IMS spectral data have been processed using sequential principal component analysis and 2-D peak distribution tests so as to investigate the molecular differentiation of tumor regions in formalin-fixed paraffin-embedded tissue biopsies of colorectal adenocarcinoma. In some of the cases fresh frozen tissue section samples were also analyzed for comparison. Multivariate analysis of spectral data revealed a specific pattern of mass ion peaks in different tumor regions that were distinguishable from the adjacent normal regions within a given specimen. Moreover, similar mass ion peaks could be detected in both FFPE and fresh-frozen tissue section samples. These significant mass ion peaks have been used to generate ion images and visualize the difference between tumor and normal regions. These specific and statistically significant ion peaks may serve as potential biomarkers for colorectal adenocarcinoma.

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Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma

Cited by 26 publications

References 34 publications

Imaging of Intact Tissue Sections: Moving beyond the Microscope

Imaging of Intact Tissue Sections: Moving beyond the Microscope

MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications

Assessment of molecular differentiation in FFPE colon adenocarcinoma tissues using PCA analysis of MALDI IMS spectral data

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