The concept of tissues appeared more than 200 years ago, since textures and attendant differences were described within the whole organism components. Instrumental developments in optics and biochemistry subsequently paved the way to transition from classical to molecular histology in order to decipher the molecular contexts associated with physiological or pathological development or function of a tissue. In 1941, Coons and colleagues performed the first systematic integrated examination of classical histology and biochemistry when his team localized pneumonia antigens in infected tissue sections. Most recently, in the early 21st century, mass spectrometry (MS) has progressively become one of the most valuable tools to analyze biomolecular compounds. Currently, sampling methods, biochemical procedures, and MS instrumentations allow scientists to perform “in depth” analysis of the protein content of any type of tissue of interest. This article reviews the salient issues in proteomics analysis of tissues. We first outline technical and analytical considerations for sampling and biochemical processing of tissues and subsequently the instrumental possibilities for proteomics analysis such as shotgun proteomics in an anatomical context. Specific attention concerns formalin fixed and paraffin embedded (FFPE) tissues that are potential “gold mines” for histopathological investigations. In all, the matrix assisted laser desorption/ionization (MALDI) MS imaging, which allows for differential mapping of hundreds of compounds on a tissue section, is currently the most striking evidence of linkage and transition between “classical” and “molecular” histology. Tissue proteomics represents a veritable field of research and investment activity for modern biomarker discovery and development for the next decade.
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References
1.
AddisMF, TancaA, PagnozziD, et al. (2009). Generation of high-quality protein extracts from formalin-fixed, paraffin-embedded tissues. Proteomics, 9, 3815–3823.
2.
AggarwalK, ChoeLH, and LeeKH. (2006). Shotgun proteomics using the iTRAQ isobaric tags. Briefings Funct Genomics Proteomics, 5, 112–120.
3.
AichlerM, ElsnerM, LudygaN, et al. (2013). Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria. J Pathol, 230, 410–419.
4.
Ait-BelkacemR, BerenguerC, VillardC, et al. (2014). MALDI imaging and in-source decay for top-down characterization of glioblastoma. Proteomics, 14, 1290–1301.
5.
Ait-BelkacemR, CalligarisD, SellamiL, et al. (2013). Tubulin isoforms identified in the brain by MALDI in-source decay. J Proteomics, 79, 172–179.
6.
AlkhasA, HoodBL, OliverK, et al. (2011). Standardization of a sample preparation and analytical workflow for proteomics of archival endometrial cancer tissue. J Proteome Res, 10, 5264–5271.
7.
AnHJ, FroehlichJW, and LebrillaCB. (2009). Determination of glycosylation sites and site-specific heterogeneity in glycoproteins. Curr Opinion Chem Biol, 13, 421–426.
8.
AvrameasS, and UrielJ. (1966). [Method of antigen and antibody labelling with enzymes and its immunodiffusion application]. C R Acad Sci Hebd Seances Acad Sci D, 262, 2543–2545.
9.
AzimzadehO, BarjaktarovicZ, AubeleM, et al. (2010). Formalin-fixed paraffin-embedded (FFPE) proteome analysis using gel-free and gel-based proteomics. J Proteome Res, 9, 4710–4720.
10.
BakerH, PatelV, MolinoloAA, et al. (2005). Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry. Oral Oncol, 41, 183–199.
11.
BeckerKF, SchottC, HippS, et al. (2007). Quantitative protein analysis from formalin-fixed tissues: Implications for translational clinical research and nanoscale molecular diagnosis. J Pathol, 211, 370–378.
12.
BoersemaPJ, MohammedS, and HeckAJ. (2009). Phosphopeptide fragmentation and analysis by mass spectrometry. J Mass Spectrom, 44, 861–878.
13.
BondarenkoPV, CheliusD, and ShalerTA. (2002). Identification and relative quantitation of protein mixtures by enzymatic digestion followed by capillary reversed-phase liquid chromatography-tandem mass spectrometry. Anal Chem, 74, 4741–4749.
14.
BonnelD, LonguespeeR, FranckJ, et al. (2011). Multivariate analyses for biomarkers hunting and validation through on-tissue bottom-up or in-source decay in MALDI-MSI: Application to prostate cancer. Anal Bioanal Chem, 401, 149–165.
15.
BonnerRF, Emmert-BuckM, ColeK, et al. (1997). Laser capture microdissection: Molecular analysis of tissue. Science, 278, 1481, 1483
16.
BoytardL, SpearR, Chinetti-GbaguidiG, et al. (2013). Role of proinflammatory CD68(+) mannose receptor(-) macrophages in peroxiredoxin-1 expression and in abdominal aortic aneurysms in humans. Arterioscler Thromb Vasc Biol, 33, 431–438.
17.
BraakmanRB, LuiderTM, MartensJW, FoekensJA, and UmarA. (2011). Laser capture microdissection applications in breast cancer proteomics. Methods Mol Biol, 755, 143–154.
18.
BraakmanRB, Tilanus-LinthorstMM, LiuNQ, et al. (2012). Optimized nLC-MS workflow for laser capture microdissected breast cancer tissue. J Proteomics, 75, 2844–2854.
19.
BuckanovichRJ, SasaroliD, O'Brien-JenkinsA, et al. (2006). Use of immuno-LCM to identify the in situ expression profile of cellular constituents of the tumor microenvironment. Cancer Biol Ther, 5, 635–642.
20.
CalligarisD, LonguespeeR, DeboisD, et al. (2013). Selected protein monitoring in histological sections by targeted MALDI-FTICR in-source decay imaging. Anal Chem, 85, 2117–2126.
21.
CalvoE, CamafeitaE, Fernandez-GutierrezB, and LopezJA. (2011). Applying selected reaction monitoring to targeted proteomics. Expert Rev Proteomics, 8, 165–173.
22.
CaprioliRM, FarmerTB, and GileJ. (1997). Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS. Anal Chem, 69, 4751–4760.
23.
CasadonteR, and CaprioliRM. (2011). Proteomic analysis of formalin-fixed paraffin-embedded tissue by MALDI imaging mass spectrometry. Nat Protoc, 6, 1695–1709.
24.
ChenJS, ChenKT, FanCW, et al. (2010). Comparison of membrane fraction proteomic profiles of normal and cancerous human colorectal tissues with gel-assisted digestion and iTRAQ labeling mass spectrometry. FEBS J, 277, 3028–3038.
25.
ChengAL, HuangWG, ChenZC, et al. (2008). Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clin Cancer Res, 14, 435–445.
26.
ChristinC, BischoffR, and HorvatovichP. (2011). Data processing pipelines for comprehensive profiling of proteomics samples by label-free LC-MS for biomarker discovery. Talanta, 83, 1209–1224.
27.
ChuWS, LiangQ, LiuJ, et al. (2005). A nondestructive molecule extraction method allowing morphological and molecular analyses using a single tissue section. Lab Invest, 85, 1416–1428.
28.
CoonsAH, and KaplanMH. (1950). Localization of antigen in tissue cells; Improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med, 91, 1–13.
29.
CoxJ, and MannM. (2009). Computational principles of determining and improving mass precision and accuracy for proteome measurements in an Orbitrap. J Am Soc Mass Spectrom, 20, 1477–1485.
30.
CravenRA, CairnsDA, ZougmanA, HarndenP, SelbyPJ, and BanksRE. (2013). Proteomic analysis of formalin-fixed paraffin-embedded renal tissue samples by label-free MS: Assessment of overall technical variability and the impact of block age. Proteomics Clin Appl, 7, 273–282.
31.
CrockettDK, LinZ, VaughnCP, LimMS, and Elenitoba-JohnsonKS. (2005). Identification of proteins from formalin-fixed paraffin-embedded cells by LC-MS/MS. Lab Invest, 85, 1405–1415.
32.
DesiereF, DeutschEW, KingNL, et al., (2006). The PeptideAtlas project. Nucleic Acids Res, 34, D655–658.
33.
DesouzaL, DiehlG, RodriguesMJ, et al. (2005). Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. J Proteome Res, 4, 377–386.
34.
DeterdingLJ, MoseleyMA, TomerKB, and JorgensonJW. (1991). Nanoscale separations combined with tandem mass spectrometry. J Chromatog, 554, 73–82.
35.
DiamentBJ, and NobleWS. (2011). Faster SEQUEST searching for peptide identification from tandem mass spectra. J Proteome Res, 10, 3871–3879.
36.
El AyedM, BonnelD, LonguespeeR, et al. (2010). MALDI imaging mass spectrometry in ovarian cancer for tracking, identifying, and validating biomarkers. Med Sci Monit, 16, BR233–245.
FendF, KremerM, and Quintanilla-MartinezL. (2000). Laser capture microdissection: Methodical aspects and applications with emphasis on immuno-laser capture microdissection. Pathobiology, 68, 209–214.
41.
FennJB, MannM, MengCK, WongSF, and WhitehouseCM. (1989). Electrospray ionization for mass spectrometry of large biomolecules. Science, 246, 64–71.
42.
FeySJ, and LarsenPM. (2001). 2D or not 2D. Two-dimensional gel electrophoresis. Curr Opinion Chem Biol, 5, 26–33.
43.
FicarroSB, McClelandML, StukenbergPT, et al. (2002). Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nature Biotechnol, 20, 301–305.
44.
FowlerCB, WaybrightTJ, VeenstraTD, O'learyTJ, and MasonJT. (2012). Pressure-assisted protein extraction: A novel method for recovering proteins from archival tissue for proteomic analysis. J Proteome Res, 11, 2602–2608.
45.
Fraenkel-ConratH, and OlcottHS. (1946). Reaction of formaldehyde with proteins; Participation of the guanidyl groups and evidence of crosslinking. J Am Chem Soc, 68, 34–37.
46.
Fraenkel-ConratH, and OlcottHS. (1948a). The reaction of formaldehyde with proteins; Cross-linking between amino and primary amide or guanidyl groups. J Am Chem Soc, 70, 2673–2684.
47.
Fraenkel-ConratH, and OlcottHS. (1948b). Reaction of formaldehyde with proteins; Cross-linking of amino groups with phenol, imidazole, or indole groups. J Biol Chem, 174, 827–843.
48.
FranckJ, LonguespeeR, WisztorskiM, et al. (2010). MALDI mass spectrometry imaging of proteins exceeding 30,000 daltons. Med Sci Monit, 16, BR293–299.
49.
FrankA, and PevznerP. (2005). PepNovo: De novo peptide sequencing via probabilistic network modeling. Anal Chem, 77, 964–973.
50.
GarbisSD, TyritzisSI, RoumeliotisT, et al. (2008). Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass spectrometry. J Proteome Res, 7, 3146–3158.
51.
GardenRW, MorozLL, MorozTP, ShippySA, and SweedlerJV. (1996). Excess salt removal with matrix rinsing: Direct peptide profiling of neurons from marine invertebrates using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Mass Spectrom, 31, 1126–1130.
52.
GiustiL, and LucacchiniA. (2013). Proteomic studies of formalin-fixed paraffin-embedded tissues. Expert Rev Proteomics, 10, 165–177.
53.
GuY, WuSL, MeyerJL, et al. (2007). Proteomic analysis of high-grade dysplastic cervical cells obtained from ThinPrep slides using laser capture microdissection and mass spectrometry. J Proteome Res, 6, 4256–4268.
54.
GuoT, WangW, RudnickPA, et al. (2007). Proteome analysis of microdissected formalin-fixed and paraffin-embedded tissue specimens. J Histochem Cytochem, 55, 763–772.
55.
GustafssonJO, OehlerMK, McCollSR, and HoffmannP. (2010). Citric acid antigen retrieval (CAAR) for tryptic peptide imaging directly on archived formalin-fixed paraffin-embedded tissue. J Proteome Res, 9, 4315–4328.
56.
HardmanM, and MakarovAA. (2003). Interfacing the orbitrap mass analyzer to an electrospray ion source. Anal Chem, 75, 1699–1705.
57.
HarrisGA, NicklayJJ, and CaprioliRM. (2013). Localized in situ hydrogel-mediated protein digestion and extraction technique for on-tissue analysis. Anal Chem, 85, 2717–2723.
58.
HatakeyamaH, KondoT, FujiiK, et al. (2006). Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer. Proteomics, 6, 6300–6316.
59.
HiggsRE, KniermanMD, GelfanovaV, ButlerJP, and HaleJE. (2005). Comprehensive label-free method for the relative quantification of proteins from biological samples. J Proteome Res, 4, 1442–1450.
60.
HillJJ, TremblayTL, PenA, et al. (2011). Identification of vascular breast tumor markers by laser capture microdissection and label-free LC-MS. J Proteome Res, 10, 2479–2493.
61.
HillenkampF, and KarasM. (1990). Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol, 193, 280–295.
62.
HirosawaM, HoshidaM, IshikawaM, and ToyaT. (1993). MASCOT: Multiple alignment system for protein sequences based on three-way dynamic programming. Computer Applic Biosci CABIOS, 9, 161–167.
63.
HosakoM, MutoT, NakamuraY, et al. (2012). Proteomic study of malignant pleural mesothelioma by laser microdissection and two-dimensional difference gel electrophoresis identified cathepsin D as a novel candidate for a differential diagnosis biomarker. J Proteomics, 75, 833–844.
64.
HwangSI, ThumarJ, LundgrenDH, et al. (2007). Direct cancer tissue proteomics: A method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues. Oncogene, 26, 65–76.
65.
IkedaK, MondenT, KanohT, et al. (1998). Extraction and analysis of diagnostically useful proteins from formalin-fixed, paraffin-embedded tissue sections. J Histochem Cytochem, 46, 397–403.
66.
JacksonSN, UgarovM, EganT, et al. (2007). MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom, 42, 1093–1098.
67.
JadoulL, MalherbeC, CalligarisD, et al. (2014). Matrix-assisted laser desorption/ionization mass spectrometry and Raman spectroscopy: An interesting complementary approach for lipid detection in biological tissues. Eur J Lipid Sci Technol, 116, In press.
68.
JiangX, FengS, TianR, YeM, and ZouH. (2007). Development of efficient protein extraction methods for shotgun proteome analysis of formalin-fixed tissues. J Proteome Res, 6, 1038–1047.
69.
JimenezCR, Van VeelenPA, LiKW, et al. (1994). Neuropeptide expression and processing as revealed by direct matrix-assisted laser desorption ionization mass spectrometry of single neurons. J Neurochem, 62, 404–407.
70.
JohannDJ, Rodriguez-CanalesJ, MukherjeeS, et al. (2009). Approaching solid tumor heterogeneity on a cellular basis by tissue proteomics using laser capture microdissection and biological mass spectrometry. J Proteome Res, 8, 2310–2318.
71.
JonesEA, DeiningerSO, HogendoornPC, DeelderAM, and McdonnellLA. (2012). Imaging mass spectrometry statistical analysis. J Proteomics, 75, 4962–4989.
72.
JonesP, CoteRG, MartensL, et al. (2006). PRIDE: A public repository of protein and peptide identifications for the proteomics community. Nucleic Acids Res, 34, D659–663.
73.
KakimotoY, TsuruyamaT, YamamotoT, et al. (2012). Novel in situ pretreatment method for significantly enhancing the signal in MALDI-TOF MS of formalin-fixed paraffin-embedded tissue sections. PLoS One, 7, e41607.
74.
KellyRT, TolmachevAV, PageJS, TangK, and SmithRD. (2010). The ion funnel: Theory, implementations, and applications. Mass Spectrom Rev, 29, 294–312.
75.
KimT, TolmachevAV, HarkewiczR, et al. (2000). Design and implementation of a new electrodynamic ion funnel. Anal Chem, 72, 2247–2255.
76.
KiyonamiR, SchoenA, PrakashA, et al. (2011). Increased selectivity, analytical precision, and throughput in targeted proteomics. Mol Cell Proteomics, 10, M110 002931.
77.
KocherT, PichlerP, MazanekM, SwartR, and MechtlerK. (2011). Altered Mascot search results by changing the m/z range of MS/MS spectra: Analysis and potential applications. Anal Bioanal Chem, 400, 2339–2347.
78.
KolbleK. (2000). The LEICA microdissection system: Design and applications. J Mol Med (Berl), 78, B24–25.
79.
KurmanRJ, and Shih IeM. (2010). The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol, 34, 433–443.
80.
LamH, DeutschEW, EddesJS, et al., (2007). Development and validation of a spectral library searching method for peptide identification from MS/MS. Proteomics, 7, 655–667.
LeongAS, MiliosJ, and DuncisCG. (1988). Antigen preservation in microwave-irradiated tissues: A comparison with formaldehyde fixation. J Pathol, 156, 275–282.
83.
LeongAS, and WrightJ. (1987). The contribution of immunohistochemical staining in tumour diagnosis. Histopathology, 11, 1295–1305.
84.
LiB, AnHJ, HedrickJL, and LebrillaCB. (2009). Collision-induced dissociation tandem mass spectrometry for structural elucidation of glycans. Methods Mol Biol, 534, 133–145.
85.
LiC, HongY, TanYX, et al. (2004). Accurate qualitative and quantitative proteomic analysis of clinical hepatocellular carcinoma using laser capture microdissection coupled with isotope-coded affinity tag and two-dimensional liquid chromatography mass spectrometry. Mol Cell Proteomics, 3, 399–409.
86.
LiC, YiH, TanYX, et al. (2008). Analysis of microdissected cells by two-dimensional LC-MS approaches. Methods Mol Biol, 428, 193–208.
87.
LilleyKS, and FriedmanDB. (2004). All about DIGE: Quantification technology for differential-display 2D-gel proteomics. Expert Rev Proteomics, 1, 401–409.
88.
LiuNQ, BraakmanRB, StinglC, et al. (2012). Proteomics pipeline for biomarker discovery of laser capture microdissected breast cancer tissue. J Mammary Gland Biol Neoplasia, 17, 155–164.
89.
LiuY, WuJ, YanG, et al. (2010). Proteomic analysis of prolactinoma cells by immuno-laser capture microdissection combined with online two-dimensional nano-scale liquid chromatography/mass spectrometry. Proteome Sci, 8, 2.
90.
LonguespeeR, BoyonC, CastellierC, et al. (2012). The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: Evidence from mass spectrometry profiling. Histochem Cell Biol, 138, 141–154.
91.
LonguespeeR, BoyonC, DesmonsA, et al. (2014a). Spectroimmunohistochemistry: A novel form of MALDI mass spectrometry imaging coupled to immunohistochemistry for tracking antibodies. Omics, 18, 132–141.
92.
LonguespeeR, GagnonH, BoyonC, et al. (2013). Proteomic analyses of serous and endometrioid epithelial ovarian cancers. Cases studies: Molecular insights of a possible histological etiology of serous ovarian cancer. Proteomics Clin Appl, 7, 337–354.
93.
LonguespeeR, TastetC, DesmonsA, et al. (2014b). HFIP extraction followed by 2D CTAB-SDS PAGE separation: A new methodology for protein identification from tissue sections after MALDI mass spectrometry profiling for personalized medicine research. OMICS, 18, 374–384.
94.
MaesE, BroeckxV, MertensI, et al. (2013). Analysis of the formalin-fixed paraffin-embedded tissue proteome: Pitfalls, challenges, and future prospectives. Amino Acids, 45, 205–218.
95.
MagdeldinS, and YamamotoT. (2012). Toward deciphering proteomes of formalin-fixed paraffin-embedded (FFPE) tissues. Proteomics, 12, 1045–1058.
96.
MaierSK, HahneH, Moghaddas GholamiA, et al. (2013). Comprehensive identification of proteins from MALDI imaging. Mol Cell Proteomics, 10, 2901–2910.
97.
MakarovA, DenisovE, KholomeevA, et al. (2006). Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal Chem, 78, 2113–2120.
98.
MakarovA, DenisovE, and LangeO. (2009). Performance evaluation of a high-field Orbitrap mass analyzer. J Am Soc Mass Spectrom, 20, 1391–1396.
99.
MannM, and KelleherNL. (2008). Precision proteomics: The case for high resolution and high mass accuracy. Proc Natl Acad Sci USA, 105, 18132–18138.
100.
MannM, and WilmM. (1994). Error-tolerant identification of peptides in sequence databases by peptide sequence tags. Anal Chem, 66, 4390–4399.
101.
MargineanI, PageJS, TolmachevAV, TangK, and SmithRD. (2010). Achieving 50% ionization efficiency in subambient pressure ionization with nanoelectrospray. Anal Chem, 82, 9344–9349.
102.
MasonDY, and SammonsR. (1978). Alkaline phosphatase and peroxidase for double immunoenzymatic labelling of cellular constituents. J Clin Pathol, 31, 454–460.
103.
MasselonC, AndersonGA, HarkewiczR, BruceJE, Pasa-TolicL, and SmithRD. (2000). Accurate mass multiplexed tandem mass spectrometry for high-throughput polypeptide identification from mixtures. Anal Chem, 72, 1918–1924.
104.
MayC, BrosseronF, ChartowskiP, MeyerHE, and MarcusK. (2012). Differential proteome analysis using 2D-DIGE. Methods Mol Biol, 893, 75–82.
105.
McDonnellLA, CorthalsGL, WillemsSM, Van RemoortereA, Van ZeijlRJ, and DeelderAM. (2010). Peptide and protein imaging mass spectrometry in cancer research. J Proteomics, 73, 1921–1944.
106.
MedingS, BalluffB, ElsnerM, et al., (2012). Tissue-based proteomics reveals FXYD3, S100A11 and GSTM3 as novel markers for regional lymph node metastasis in colon cancer. J Pathol, 228, 459–470.
107.
MedingS, MartinK, GustafssonOJ, et al. (2013). Tryptic peptide reference data sets for MALDI imaging mass spectrometry on formalin-fixed ovarian cancer tissues. J Proteome Res, 12, 308–315.
108.
MichalskiA, DamocE, HauschildJP, et al. (2011). Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer. Mol Cell Proteomics, 10, M111 011015.
109.
MickeP, OstmanA, LundebergJ, and PontenF. (2005). Laser-assisted cell microdissection using the PALM system. Methods Mol Biol, 293, 151–166.
110.
MuraokaS, KumeH, WatanabeS, et al. (2012). Strategy for SRM-based verification of biomarker candidates discovered by iTRAQ method in limited breast cancer tissue samples. J Proteome Res, 11, 4201–4210.
111.
NadjiM. (1986). Immunoperoxidase techniques. I. Facts and artifacts. Am J Dermatopathol, 8, 32–36.
112.
NagarajN, D'souzaRC, CoxJ, OlsenJV, and MannM. (2010). Feasibility of large-scale phosphoproteomics with higher energy collisional dissociation fragmentation. J Proteome Res, 9, 6786–6794.
113.
NakamuraN, RuebelK, JinL, QianX, ZhangH, and LloydRV. (2007). Laser capture microdissection for analysis of single cells. Methods Mol Med, 132, 11–18.
114.
NakanePK. (1968). Simultaneous localization of multiple tissue antigens using the peroxidase-labeled antibody method: A study on pituitary glands of the rat. J Histochem Cytochem, 16, 557–560.
115.
NakanePK, and PierceGBJr. (1966). Enzyme-labeled antibodies: Preparation and application for the localization of antigens. J Histochem Cytochem, 14, 929–931.
116.
NakataniS, WeiM, IshimuraE, et al. (2012). Proteome analysis of laser microdissected glomeruli from formalin-fixed paraffin-embedded kidneys of autopsies of diabetic patients: Nephronectin is associated with the development of diabetic glomerulosclerosis. Nephrol Dial Transplant, 27, 1889–1897.
117.
NarumiR, MurakamiT, KugaT, et al. (2012). A strategy for large-scale phosphoproteomics and SRM-based validation of human breast cancer tissue samples. J Proteome Res, 11, 5311–5322.
118.
NazarianJ, SantiM, HathoutY, and MacdonaldTJ. (2008). Protein profiling of formalin fixed paraffin embedded tissue: Identification of potential biomarkers for pediatric brainstem glioma. Proteomics Clin Appl, 2, 915–924.
119.
NeilsonKA, AliNA, MuralidharanS, et al.,(2011). Less label, more free: Approaches in label-free quantitative mass spectrometry. Proteomics, 11, 535–553.
120.
NirmalanNJ, HarndenP, SelbyPJ, and BanksRE. (2008). Mining the archival formalin-fixed paraffin-embedded tissue proteome: opportunities and challenges. Mol Biosyst, 4, 712–720.
121.
NirmalanNJ, HarndenP, SelbyPJ, and BanksRE. (2009). Development and validation of a novel protein extraction methodology for quantitation of protein expression in formalin-fixed paraffin-embedded tissues using western blotting. J Pathol, 217, 497–506.
122.
NirmalanNJ, HughesC, PengJ, et al. (2011). Initial development and validation of a novel extraction method for quantitative mining of the formalin-fixed, paraffin-embedded tissue proteome for biomarker investigations. J Proteome Res, 10, 896–906.
123.
NishimuraT, NomuraM, TojoH, et al. (2010). Proteomic analysis of laser-microdissected paraffin-embedded tissues: (2) MRM assay for stage-related proteins upon non-metastatic lung adenocarcinoma. J Proteomics, 73, 1100–1110.
124.
OdaY, NagasuT, and ChaitBT. (2001). Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nature Biotechnol, 19, 379–382.
125.
OlsenJV, SchwartzJC, Griep-RamingJ, et al, (2009). A dual pressure linear ion trap Orbitrap instrument with very high sequencing speed. Mol Cell Proteomics, 8, 2759–2769.
126.
OstasiewiczP, ZielinskaDF, MannM, and WisniewskiJR. (2010). Proteome, phosphoproteome, and N-glycoproteome are quantitatively preserved in formalin-fixed paraffin-embedded tissue and analyzable by high-resolution mass spectrometry. J Proteome Res, 9, 3688–3700.
127.
PageJS, TangK, KellyRT, and SmithRD. (2008). Subambient pressure ionization with nanoelectrospray source and interface for improved sensitivity in mass spectrometry. Anal Chem, 80, 1800–1805.
128.
PageJS, TolmachevAV, TangK, and SmithRD. (2006). Theoretical and experimental evaluation of the low m/z transmission of an electrodynamic ion funnel. J Am Soc Mass Spectrom, 17, 586–592.
129.
Palmer-ToyDE, KrastinsB, SarracinoDA, NadolJBJr., and MerchantSN. (2005). Efficient method for the proteomic analysis of fixed and embedded tissues. J Proteome Res, 4, 2404–2411.
130.
Palmer-ToyDE, SarracinoDA, SgroiD, LevangieR, and LeopoldPE. (2000). Direct acquisition of matrix-assisted laser desorption/ionization time-of-flight mass spectra from laser capture microdissected tissues. Clin Chem, 46, 1513–1516.
131.
PanS, ChenR, StevensT, et al. (2011). Proteomics portrait of archival lesions of chronic pancreatitis. PLoS One, 6, e27574.
132.
PanchaudA, JungS, ShafferSA, AitchisonJD, and GoodlettDR. (2011). Faster, quantitative, and accurate precursor acquisition independent from ion count. Anal Chem, 83, 2250–2257.
133.
PanchaudA, ScherlA, ShafferSA, et al. (2009). Precursor acquisition independent from ion count: How to dive deeper into the proteomics ocean. Anal Chem, 81, 6481–6488.
134.
PietersenCY, LimMP, and WooTU. (2009). Obtaining high quality RNA from single cell populations in human postmortem brain tissue. J Vis Exp, 30, 1444.
135.
PrietoDA, HoodBL, DarflerMM, et al. (2005). Liquid Tissue: Proteomic profiling of formalin-fixed tissues. Biotechniques Suppl, 38, 32–35.
136.
RezaulK, ThumarJK, LundgrenDH, et al. (2010). Differential protein expression profiles in estrogen receptor-positive and -negative breast cancer tissues using label-free quantitative proteomics. Genes Cancer, 1, 251–271.
137.
RomppA, and SpenglerB. (2013). Mass spectrometry imaging with high resolution in mass and space. Histochem Cell Biol, 139, 759–783.
138.
SandersME, DiasEC, XuBJ, et al. (2008). Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. J Proteome Res, 7, 1500–1507.
139.
ShafferSA, PriorDC, AndersonGA, UdsethHR, and SmithRD. (1998). An ion funnel interface for improved ion focusing and sensitivity using electrospray ionization mass spectrometry. Anal Chem, 70, 4111–4119.
140.
ShekouhAR, ThompsonCC, PrimeW, et al, (2003). Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma. Proteomics, 3, 1988–2001.
141.
ShiH, HoodKA, HayesMT, and StubbsRS. (2011). Proteomic analysis of advanced colorectal cancer by laser capture microdissection and two-dimensional difference gel electrophoresis. J Proteomics, 75, 339–351.
142.
ShiSR, LiuC, BalgleyBM, LeeC, and TaylorCR. (2006). Protein extraction from formalin-fixed, paraffin-embedded tissue sections: Quality evaluation by mass spectrometry. J Histochem Cytochem, 54, 739–743.
143.
ShvartsburgAA, SeimTA, DanielsonWF, et al. (2013). High-definition differential ion mobility spectrometry with resolving power up to 500. J Am Soc Mass Spectrom, 24, 109–114.
144.
ShvartsburgAA, SingerD, SmithRD, and HoffmannR. (2011). Ion mobility separation of isomeric phosphopeptides from a protein with variant modification of adjacent residues. Anal Chem, 83, 5078–5085.
145.
SingerSJ. (1959). Preparation of an electron-dense antibody conjugate. Nature, 183, 1523–1524.
146.
SkvortsovS, SchaferG, StasykT, et al. (2011). Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker. J Proteome Res, 10, 259–268.
147.
StahlB, LinosA, KarasM, HillenkampF, and SteupM. (1997). Analysis of fructans from higher plants by matrix-assisted laser desorption/ionization mass spectrometry. Anal Biochem, 246, 195–204.
148.
StauberJ, AyedME, WisztorskiM, SalzetM, and FournierI. (2010). Specific MALDI-MSI: Tag-Mass. Methods Mol Biol, 656, 339–361.
149.
SternbergerLA, HardyPHJr., CuculisJJ, and MeyerHG. (1970). The unlabeled antibody enzyme method of immunohistochemistry: Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem, 18, 315–333.
150.
StinglC, Van VilsterenFG, GuzelC, et al. (2011). Reproducibility of protein identification of selected cell types in Barrett's esophagus analyzed by combining laser-capture microdissection and mass spectrometry. J Proteome Res, 10, 288–298.
151.
SugiharaY, TaniguchiH, KushimaR, et al. (2013). Laser microdissection and two-dimensional difference gel electrophoresis reveal proteomic intra-tumor heterogeneity in colorectal cancer. J Proteomics, 78, 134–147.
152.
SwansonPE. (1997). HIERanarchy: The state of the art in immunohistochemistry. Am J Clin Pathol, 107, 139–140.
153.
TabbDL, FernandoCG, and ChambersMC. (2007). MyriMatch: Highly accurate tandem mass spectral peptide identification by multivariate hypergeometric analysis. J Proteome Res, 6, 654–661.
154.
TabbDL, MaZQ, MartinDB, HamAJ, and ChambersMC. (2008). DirecTag: Accurate sequence tags from peptide MS/MS through statistical scoring. J Proteome Res, 7, 3838–3846.
155.
TabbDL, SarafA, and YatesJR, 3rd. (2003). GutenTag: High-throughput sequence tagging via an empirically derived fragmentation model. Anal Chem, 75, 6415–6421.
156.
TanakaK, WakiH, IdoY, et al. (1988). Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom, 2, 151–153.
157.
TangK, PageJS, MargineanI, KellyRT, and SmithRD. (2011). Improving liquid chromatography-mass spectrometry sensitivity using a subambient pressure ionization with nanoelectrospray (SPIN) interface. J Am Soc Mass Spectrom, 22, 1318–1325.
158.
TangreaMA, MukherjeeS, GaoB, et al. (2011). Effect of immunohistochemistry on molecular analysis of tissue samples: Implications for microdissection technologies. J Histochem Cytochem, 59, 591–600.
159.
ThakurD, RejtarT, WangD, et al. (2011). Microproteomic analysis of 10,000 laser captured microdissected breast tumor cells using short-range sodium dodecyl sulfate-polyacrylamide gel electrophoresis and porous layer open tubular liquid chromatography tandem mass spectrometry. J Chromatogr A, 1218, 8168–8174.
160.
TianY, GurleyK, MeanyDL, KempCJ, and ZhangH. (2009). N-linked glycoproteomic analysis of formalin-fixed and paraffin-embedded tissues. J Proteome Res, 8, 1657–1662.
161.
UmarA, KangH, TimmermansAM, LookMP, et al. (2009). Identification of a putative protein profile associated with tamoxifen therapy resistance in breast cancer. Mol Cell Proteomics, 8, 1278–1294.
162.
UmarA, LuiderTM, FoekensJA, and Pasa-TolicL. (2007). NanoLC-FT-ICR MS improves proteome coverage attainable for approximately 3000 laser-microdissected breast carcinoma cells. Proteomics, 7, 323–329.
163.
Van RemoortereA, Van ZeijlRJ, Van Den OeverN, et al. (2010). MALDI imaging and profiling MS of higher mass proteins from tissue. J Am Soc Mass Spectrom, 21, 1922–1929.
164.
Van StrienFJ, JespersenS, Van Der GreefJ, JenksBG, and RoubosEW. (1996). Identification of POMC processing products in single melanotrope cells by matrix-assisted laser desorption/ionization mass spectrometry. FEBS Lett, 379, 165–170.
165.
VenableJD, DongMQ, WohlschlegelJ, DillinA, and YatesJR. (2004). Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra. Nature Meth, 1, 39–45.
166.
VizcainoJA, CoteR, ReisingerF, et al. (2009). A guide to the Proteomics Identifications Database proteomics data repository. Proteomics, 9, 4276–4283.
167.
VogtA, FuerholznerB, KinklN, BoldtK, and UeffingM. (2013). Isotope coded protein labeling coupled immunoprecipitation (ICPL-IP): A novel approach for quantitative protein complex analysis from native tissue. Mol Cell Proteomics, 12, 1395–1406.
168.
WangG, WuWW, ZengW, ChouCL, and ShenRF. (2006). Label-free protein quantification using LC-coupled ion trap or FT mass spectrometry: Reproducibility, linearity, and application with complex proteomes. J Proteome Res, 5, 1214–1223.
169.
WangLN, TongSW, HuHD, et al. (2012). Quantitative proteome analysis of ovarian cancer tissues using a iTRAQ approach. J Cell Biochem, 113, 3762–3772.
170.
WellsJM, and McluckeySA. (2005). Collision-induced dissociation (CID) of peptides and proteins. Methods Enzymol, 402, 148–185.
171.
WiesnerJ, PremslerT, and SickmannA. (2008). Application of electron transfer dissociation (ETD) for the analysis of posttranslational modifications. Proteomics, 8, 4466–4483.
172.
WillemsSM, Van RemoortereA, Van ZeijlR, DeelderAM, McdonnellLA, and HogendoornPC. (2010). Imaging mass spectrometry of myxoid sarcomas identifies proteins and lipids specific to tumour type and grade, and reveals biochemical intratumour heterogeneity. J Pathol, 222, 400–409.
173.
WisniewskiJR, DusK, and MannM. (2013). Proteomic workflow for analysis of archival formalin-fixed and paraffin-embedded clinical samples to a depth of 10 000 proteins. Proteomics Clin Appl, 7, 225–233.
174.
WisniewskiJR, OstasiewiczP, and MannM. (2011). High recovery FASP applied to the proteomic analysis of microdissected formalin fixed paraffin embedded cancer tissues retrieves known colon cancer markers. J Proteome Res, 10, 3040–3049.
175.
WisztorskiM, FatouB, FranckJ, et al. (2013). Microproteomics by liquid extraction surface analysis: Application to FFPE tissue to study the fimbria region of tubo-ovarian cancer. Proteomics Clin Appl, 7, 234–240.
176.
WongKF, and LukJM. (2012). Discovery of lamin B1 and vimentin as circulating biomarkers for early hepatocellular carcinoma. Methods Mol Biol, 909, 295–310.
177.
XuBJ, CaprioliRM, SandersME, and JensenRA. (2002). Direct analysis of laser capture microdissected cells by MALDI mass spectrometry. J Am Soc Mass Spectrom, 13, 1292–1297.
178.
XuBJ, LiJ, BeauchampRD, et al. (2009). Identification of early intestinal neoplasia protein biomarkers using laser capture microdissection and MALDI MS. Mol Cell Proteomics, 8, 936–945.
179.
XuBJ, ShyrY, LiangX, et al. (2005). Proteomic patterns and prediction of glomerulosclerosis and its mechanisms. J Am Soc Nephrol, 16, 2967–2975.
180.
XuH, YangL, WangW, et al. (2008). Antigen retrieval for proteomic characterization of formalin-fixed and paraffin-embedded tissues. J Proteome Res, 7, 1098–1108.
181.
YaoH, ZhangZ, XiaoZ, et al. (2009). Identification of metastasis associated proteins in human lung squamous carcinoma using two-dimensional difference gel electrophoresis and laser capture microdissection. Lung Cancer, 65, 41–48.
182.
YatesJR, 3rd, MorganSF, GatlinCL, GriffinPR, and EngJK. (1998). Method to compare collision-induced dissociation spectra of peptides: Potential for library searching and subtractive analysis. Anal Chem, 70, 3557–3565.
183.
ZangL, Palmer ToyD, HancockWS, SgroiDC, and KargerBL. (2004). Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling. J Proteome Res, 3, 604–612.
184.
ZanniKL, and ChanGK. (2011). Laser capture microdissection: Understanding the techniques and implications for molecular biology in nursing research through analysis of breast cancer tumor samples. Biol Res Nurs, 13, 297–305.
185.
ZhangD, TaiLK, WongLL, ChiuLL, SethiSK, and KoayES. (2005). Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer. Mol Cell Proteomics, 4, 1686–1696.
186.
ZhangH, LiXJ, MartinDB, and AebersoldR. (2003). Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature Biotechnol, 21, 660–666.
187.
ZhangJ, XinL, ShanB, et al. (2012). PEAKS DB: De novo sequencing assisted database search for sensitive and accurate peptide identification. Mol Cell Proteomics, 11, M111 010587.
188.
ZhangY, TangH, CaiJ, et al. (2011). Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett, 303, 47–55.
189.
ZhouG, LiH, DecampD, et al. (2002). 2D differential in-gel electrophoresis for the identification of esophageal scans cell cancer-specific protein markers. Mol Cell Proteomics, 1, 117–124.
190.
ZhouH, WattsJD, and AebersoldR. (2001). A systematic approach to the analysis of protein phosphorylation. Nature Biotechnol, 19, 375–378.
191.
ZhuJ, NieS, WuJ, and LubmanDM. (2013). Target proteomic profiling of frozen pancreatic CD24+ adenocarcinoma tissues by immuno-laser capture microdissection and nano-LC-MS/MS. J Proteome Res, 12, 2791–2804.
