Approaching MALDI molecular imaging for clinical proteomic research: current state and fields of application

MALDI imaging mass spectrometry (‘MALDI imaging’) is an increasingly recognized technique for biomarker research. After years of method development in the scientific community, the technique is now increasingly applied in clinical research. In this article, we discuss the use of MALDI imaging in clinical proteomics and put it in context with classical proteomics techniques. We also highlight a number of upcoming challenges for personalized medicine, development of targeted therapies and diagnostic molecular pathology where MALDI imaging could help.

[1]  P. Chaurand,et al.  Processing MALDI Mass Spectra to Improve Mass Spectral Direct Tissue Analysis. , 2007, International journal of mass spectrometry.

[2]  Sandra Rauser,et al.  MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology , 2008, Histochemistry and Cell Biology.

[3]  N. Pavlidis,et al.  Cancer of unknown primary (CUP). , 2005, Critical reviews in oncology/hematology.

[4]  P. Chaurand,et al.  Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections , 2008, Journal of the American Society for Mass Spectrometry.

[5]  U. Köthe,et al.  Toward digital staining using imaging mass spectrometry and random forests. , 2009, Journal of proteome research.

[6]  B. Spengler,et al.  Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cells. , 2010, Rapid communications in mass spectrometry : RCM.

[7]  Henry Z. Montes,et al.  TNM Classification of Malignant Tumors, 7th edition , 2010 .

[8]  P. Svenningsson,et al.  Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. , 2006, Journal of proteome research.

[9]  Cameron C. Jones,et al.  Differential efficacy of combined therapy with radiation and AEE788 in high and low EGFR-expressing androgen-independent prostate tumor models. , 2008, International journal of radiation oncology, biology, physics.

[10]  Yu Shyr,et al.  Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. , 2005, Cancer research.

[11]  Benoit M Dawant,et al.  Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging , 2008, Nature Methods.

[12]  Patrick Ducoroy,et al.  Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker. , 2007, Journal of proteome research.

[13]  Gerhard Jakse,et al.  Identifying prostate carcinoma by MALDI-Imaging. , 2007, International journal of molecular medicine.

[14]  Yu Shyr,et al.  Proteomic patterns and prediction of glomerulosclerosis and its mechanisms. , 2005, Journal of the American Society of Nephrology : JASN.

[15]  Jonathan V Sweedler,et al.  Massively parallel sample preparation for the MALDI MS analyses of tissues. , 2006, Analytical chemistry.

[16]  L. Sobin,et al.  TNM Classification of Malignant Tumours , 1987, UICC International Union Against Cancer.

[17]  Richard M. Caprioli,et al.  Molecular Assessment of the Tumor Protein Microenvironment Using Imaging Mass Spectrometry , 2006 .

[18]  Michelle L. Reyzer,et al.  MALDI imaging mass spectrometry: molecular snapshots of biochemical systems , 2007, Nature Methods.

[19]  Baogang J. Xu,et al.  Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. , 2008, Journal of proteome research.

[20]  I. Fournier,et al.  On-tissue protein identification and imaging by MALDI-Ion mobility mass spectrometry , 2010, Journal of the American Society for Mass Spectrometry.

[21]  Erik K. Malm,et al.  A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics* , 2005, Molecular & Cellular Proteomics.

[22]  Francesca M. Buffa,et al.  Multiple biomarker tissue microarrays: bioinformatics and practical approaches , 2008, Cancer and Metastasis Reviews.

[23]  Richard M Caprioli,et al.  Instrument design and characterization for high resolution MALDI-MS imaging of tissue sections. , 2007, Journal of mass spectrometry : JMS.

[24]  Walter A. Korfmacher,et al.  Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry. , 2003, Journal of mass spectrometry : JMS.

[25]  P. Chaurand,et al.  Liquid chromatography-tandem and MALDI imaging mass spectrometry analyses of RCL2/CS100-fixed, paraffin-embedded tissues: proteomics evaluation of an alternate fixative for biomarker discovery. , 2009, Journal of proteome research.

[26]  R. Caprioli,et al.  In situ molecular imaging of proteins in tissues using mass spectrometry , 2008, Analytical and bioanalytical chemistry.

[27]  Richard M Caprioli,et al.  Early Changes in Protein Expression Detected by Mass Spectrometry Predict Tumor Response to Molecular Therapeutics , 2004, Cancer Research.

[28]  R. Banks,et al.  Laser Capture Microdissection for Proteome Analysis , 2003, Current protocols in protein science.

[29]  Michelle L. Reyzer,et al.  Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. , 2003, Journal of mass spectrometry : JMS.

[30]  T. Nielsen,et al.  Tissue microarrays in clinical oncology. , 2008, Seminars in radiation oncology.

[31]  P. Chaurand,et al.  Monitoring Mouse Prostate Development by Profiling and Imaging Mass Spectrometry*S , 2008, Molecular & Cellular Proteomics.

[32]  Yu Shyr,et al.  Proteomic patterns of tumour subsets in non-small-cell lung cancer , 2003, The Lancet.

[33]  Jonathan V Sweedler,et al.  MALDI mass spectrometric imaging using the stretched sample method to reveal neuropeptide distributions in aplysia nervous tissue. , 2009, Analytical chemistry.

[34]  Pamela K. Kreeger,et al.  Cancer systems biology: a network modeling perspective , 2009, Carcinogenesis.

[35]  M. Setou,et al.  In situ proteomics with imaging mass spectrometry and principal component analysis in the Scrapper‐knockout mouse brain , 2008, Proteomics.

[36]  P. Dorrestein,et al.  Imaging Mass Spectrometry of Natural Products , 2010 .

[37]  Richard M Caprioli,et al.  Molecular analysis of tumor margins by MALDI mass spectrometry in renal carcinoma. , 2010, Journal of proteome research.

[38]  I. Fournier,et al.  Direct analysis and MALDI imaging of formalin-fixed, paraffin-embedded tissue sections. , 2007, Journal of proteome research.

[39]  M. Emmert-Buck,et al.  Approaching solid tumor heterogeneity on a cellular basis by tissue proteomics using laser capture microdissection and biological mass spectrometry. , 2009, Journal of proteome research.

[40]  Richard M Caprioli,et al.  A Novel Histology-directed Strategy for MALDI-MS Tissue Profiling That Improves Throughput and Cellular Specificity in Human Breast Cancer* , 2006, Molecular & Cellular Proteomics.

[41]  Richard M Caprioli,et al.  New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. , 2006, Journal of proteome research.

[42]  Jonathan V Sweedler,et al.  Characterizing peptides in individual mammalian cells using mass spectrometry , 2007, Nature Protocols.

[43]  Andrea Urbani,et al.  Protein unlocking procedures of formalin‐fixed paraffin‐embedded tissues: Application to MALDI‐TOF Imaging MS investigations , 2008, Proteomics.

[44]  Fred A Hamprecht,et al.  Concise representation of mass spectrometry images by probabilistic latent semantic analysis. , 2008, Analytical chemistry.

[45]  Jeffrey S. Morris,et al.  Laser capture sampling and analytical issues in proteomics , 2007, Expert review of proteomics.

[46]  Manfred Dietel,et al.  Personalized medicine and development of targeted therapies: the upcoming challenge for diagnostic molecular pathology. A review , 2006, Virchows Archiv.

[47]  M. Stoeckli,et al.  Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues , 2001, Nature Medicine.

[48]  Maxence Wisztorski,et al.  Molecular MALDI imaging: An emerging technology for neuroscience studies , 2008, Developmental neurobiology.

[49]  C.E. Shannon,et al.  Communication in the Presence of Noise , 1949, Proceedings of the IRE.

[50]  Yu Shyr,et al.  Identification of Early Intestinal Neoplasia Protein Biomarkers Using Laser Capture Microdissection and MALDI MS*S , 2009, Molecular & Cellular Proteomics.

[51]  Enrique Viguera,et al.  Multitissue array review: a chronological description of tissue array techniques, applications and procedures. , 2006, Pathology, research and practice.

[52]  Sören-Oliver Deininger,et al.  MALDI imaging combined with hierarchical clustering as a new tool for the interpretation of complex human cancers. , 2008, Journal of proteome research.

[53]  Jean-Charles Sanchez,et al.  Proteomics: new perspectives, new biomedical opportunities , 2000, The Lancet.

[54]  M. Clench,et al.  Novel molecular tumour classification using MALDI–mass spectrometry imaging of tissue micro-array , 2010, Analytical and bioanalytical chemistry.

[55]  Detlev Suckau,et al.  Classification of HER2 receptor status in breast cancer tissues by MALDI imaging mass spectrometry. , 2010, Journal of proteome research.

[56]  J. Walker,et al.  Automated solvent-free matrix deposition for tissue imaging by mass spectrometry. , 2010, Analytical chemistry.

[57]  N. Pavlidis,et al.  Carcinoma of Unknown Primary (CUP) , 2014 .

[58]  S. Pennington,et al.  Protein and peptides in pictures: Imaging with MALDI mass spectrometry , 2008, Proteomics.

[59]  C. López-Otín,et al.  Emerging roles of proteases in tumour suppression , 2007, Nature Reviews Cancer.

[60]  Daohai Zhang,et al.  Proteomic Study Reveals That Proteins Involved in Metabolic and Detoxification Pathways Are Highly Expressed in HER-2/neu-positive Breast Cancer* , 2005, Molecular & Cellular Proteomics.

[61]  R. Heeren,et al.  A concise review of mass spectrometry imaging. , 2010, Journal of chromatography. A.

[62]  Markus Stoeckli,et al.  Molecular imaging of amyloid beta peptides in mouse brain sections using mass spectrometry. , 2002, Analytical biochemistry.

[63]  D. Carter.  TNM Classification of Malignant Tumors , 1998 .

[64]  Zoltan Takats,et al.  Histology by mass spectrometry: label-free tissue characterization obtained from high-accuracy bioanalytical imaging. , 2010, Angewandte Chemie.

[65]  Eric P. Skaar,et al.  Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses , 2008, Science.

[66]  M. Clench,et al.  Detergent addition to tryptic digests and ion mobility separation prior to MS/MS improves peptide yield and protein identification for in situ proteomic investigation of frozen and formalin‐fixed paraffin‐embedded adenocarcinoma tissue sections , 2009, Proteomics.

[67]  R. Caprioli,et al.  Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. , 2007, Journal of mass spectrometry : JMS.

[68]  H. Shim,et al.  Molecular proteomics imaging of tumor interfaces by mass spectrometry. , 2010, Journal of proteome research.

[69]  M. Basik,et al.  Microarrays as validation strategies in clinical samples: tissue and protein microarrays. , 2006, Omics : a journal of integrative biology.

[70]  P. Chaurand,et al.  Profiling proteins from azoxymethane‐induced colon tumors at the molecular level by matrix‐assisted laser desorption/ionization mass spectrometry , 2001, Proteomics.

[71]  Pierre P Massion,et al.  High‐throughput proteomic analysis of formalin‐fixed paraffin‐embedded tissue microarrays using MALDI imaging mass spectrometry , 2008, Proteomics.

[72]  Mats Borén,et al.  Stopping the clock on proteomic degradation by heat treatment at the point of tissue excision , 2010, Proteomics.

[73]  A. Olshen,et al.  Differential exoprotease activities confer tumor-specific serum peptidome patterns. , 2005, The Journal of clinical investigation.

[74]  M. Gurcan,et al.  Imaging mass spectrometry analysis for follicular lymphoma grading , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[75]  I. Fournier,et al.  On-tissue N-terminal peptide derivatizations for enhancing protein identification in MALDI mass spectrometric imaging strategies. , 2009, Analytical chemistry.

[76]  M. Stoeckli,et al.  Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis. , 2005, Analytical chemistry.

[77]  F. Pontén,et al.  Antibody-based Proteomics for Human Tissue Profiling , 2005, Molecular & Cellular Proteomics.

[78]  I. Fournier,et al.  MALDI imaging of formalin-fixed paraffin-embedded tissues: application to model animals of Parkinson disease for biomarker hunting. , 2008, Journal of proteome research.

[79]  M. Snel,et al.  High-spatial resolution matrix-assisted laser desorption ionization imaging analysis of glucosylceramide in spleen sections from a mouse model of Gaucher disease. , 2010, Analytical chemistry.

[80]  Maxence Wisztorski,et al.  New developments in MALDI imaging for pathology proteomic studies. , 2007, Current pharmaceutical design.

[81]  I. Fournier,et al.  Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics , 2008, Expert review of proteomics.

[82]  Benoit M Dawant,et al.  Three-dimensional visualization of protein expression in mouse brain structures using imaging mass spectrometry , 2005, Journal of the American Society for Mass Spectrometry.

[83]  R. Banks,et al.  Laser capture microdissection and proteomics: Possibilities and limitation , 2001, Proteomics.

[84]  Richard M Caprioli,et al.  Molecular profiling of experimental Parkinson's disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. , 2004, Journal of proteome research.

[85]  L. Quinton,et al.  Mass spectrometry imaging of rat brain sections: nanomolar sensitivity with MALDI versus nanometer resolution by TOF–SIMS , 2010, Analytical and bioanalytical chemistry.

[86]  Ariel Y Deutch,et al.  Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction , 2008, Nature Methods.

[87]  Bart De Moor,et al.  Prospective Exploration of Biochemical Tissue Composition via Imaging Mass Spectrometry Guided by Principal Component Analysis , 2006, Pacific Symposium on Biocomputing.

[88]  R. Caprioli,et al.  Identification of Markers of Taxane Sensitivity Using Proteomic and Genomic Analyses of Breast Tumors from Patients Receiving Neoadjuvant Paclitaxel and Radiation , 2010, Clinical Cancer Research.

[89]  Lisa H Cazares,et al.  Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue , 2009, Clinical Cancer Research.

[90]  N. Karp,et al.  Addressing Accuracy and Precision Issues in iTRAQ Quantitation* , 2010, Molecular & Cellular Proteomics.

[91]  J. Lam,et al.  Tissue Array-Based Predictions of Pathobiology, Prognosis, and Response to Treatment for Renal Cell Carcinoma Therapy , 2004, Clinical Cancer Research.

[92]  P. Lescuyer,et al.  Imaging mass spectrometry using peptide isoelectric focusing. , 2008, Rapid communications in mass spectrometry : RCM.

[93]  I. Fournier,et al.  Improving tissue preparation for matrix-assisted laser desorption ionization mass spectrometry imaging. Part 1: using microspotting. , 2009, Analytical chemistry.

[94]  M. Clench,et al.  MALDI-ion mobility separation-mass spectrometry imaging of glucose-regulated protein 78 kDa (Grp78) in human formalin-fixed, paraffin-embedded pancreatic adenocarcinoma tissue sections. , 2009, Journal of proteome research.

[95]  Dean Billheimer,et al.  Integrating histology and imaging mass spectrometry. , 2004, Analytical chemistry.

[96]  Roy A Jensen,et al.  Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. , 2004, The American journal of pathology.

[97]  Hanno Langen,et al.  Biomarker Discovery by Imaging Mass Spectrometry , 2006, Molecular & Cellular Proteomics.