{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Mgf":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9220.mgf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P2031.mgf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9361.mgf","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P3105.mgf"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150728_Benign_08P2031_RHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150723_Cancer_08P5640_RHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P3105.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9220.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/LHSsectn2_Benign2Adjacent_OBP5627.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P2031.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150730_Cancer_08P9220_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150727_Benign_08P3105_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150723_BenignLHS_08P5640_RHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150727_Benign_08P3105-RHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150805_Benign_08P15660_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P2031.dat","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9361.dat","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9220.dat","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P9361.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150805_Cancer_08P15660_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150724_HCCA_BenignLHS_08P7070_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150806_Benign_08P9361_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150724_HCCA_Cancer_08P7070_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150727_Cancer_08P3105_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150722_Cancer_08P5640_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/08P3105.dat","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150728_Cancer_08P2031_RHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/LHSsectn_Cancer_OBP5627.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150724_HCCA_BenignRHS_08P7070_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150730_Benign_08P9220_LHS.imzML","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/05/PXD013397/150806_Cancer_08P9361_LHS.imzML"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["robert.baxter@sydney.edu.au"],"submitter":["Robert Baxter"],"technology_type":["mass spectrometry imaging","Mass Spectrometry"],"disease":["Triple-receptor Negative Breast Cancer","Breast Cancer"],"software":[""],"submitter_keywords":["Human","Maldi imaging","Triple-negative","Breast cancer"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD013397"],"tissue":["Epithelial Cell","Breast Cancer Cell"],"sample_protocol":["Patient specimens Ten FFPE blocks containing TNBC tissue were obtained from the Department of Surgical Pathology, University of Sydney, NSW, Australia. Sections of 10 µm were cut with a microtome and mounted onto ITO treated glass slides. Adjacent sections were mounted onto conventional glass slides for hematoxylin and eosin staining to permit histopathology evaluation of the tumor location.    Slide preparation for MSI analysis Mounted FFPE sections were deparaffinized in two changes of xylene (15 min each) and hydrated with a graded series of ethanol dips (2 min each: 100%, 100%, 95%, 70%, 0%, 0%). Antigen retrieval was performed with 10 mM citrate acid buffer pH 6.0 using a Dako Cytomation Pascal pressure cooker (Model S2800, Dako, NSW, Australia), at 121°C for 16 min followed by 90°C for 16 min. Sections were then cooled to room temperature and washed with 10 mM ammonium bicarbonate (ABC) for 1 min. The ITO mounted tissue was digested using the ImagePrep automatic vibrational nebulizer (Bruker Daltonics) spraying a 0.1 µg/µL solution of trypsin in 20 mM ABC. Spraying was performed at room temperature using the default “Trypsin Deposition” method. ITO slides were then incubated 2 h at 40°C in a humidified container. Internal calibrants were sprayed onto the slides using the “Trypsin Deposition” method and matrix solution of 7 mg/mL CHCA in 50% ACN/0.2% TFA was then sprayed using standard CHCA settings.   Peptide extraction for LC-MALDI analysis  To extract tissues for LC-MALDI peptide analysis, slides were subjected to antigen retrieval and vacuum dried for 1 h, then the tissue was removed from the slide, placed in a 1.5 mL tube in 500 µl of 0.2% RapiGest SF surfactant in 50 mM ABC, vortexed, sonicated 10 min, then tris(2-carboxyethyl)phosphine was added to a final concentration of 5 mM. Samples were heated for 30 min at 60°C, cooled to room temperature, and alkylated with 15 mM iodoacetamide for 30 min in the dark. BCA assays were performed to determine protein concentrations. Trypsin was added at a 1:50 ratio relative to protein concentration, and incubated overnight at 37°C. TFA was added to the digested protein samples to a concentration of 0.5% (pH <2) and incubated at 37°C for 40 min. Samples were centrifuged at 13,200 rpm for 10 min, and supernatants were collected and freeze-dried. Samples were reconstituted with 2% ACN/0.1% TFA, centrifuged at 13,200 rpm, and supernatants were passed through a 0.2 µm filter into HPLC vials.   MALDI MS imaging data  Each of the ten H&E stained sections was examined by a pathologist and regions of each section were designated cancerous, benign or common (both cancerous and benign tissue present). Adjacent sections on ITO slides were used to acquire imaging mass spectra from each region. Spectra were acquired using a Bruker UltrafleXtreme TOF-TOF MALDI mass spectrometer equipped with a SmartBeam 2000 Hz laser (Bruker Daltonics) in positive ion reflectron mode. Mass spectra were collected in the m/z range 700-3500, with a spatial resolution of 50 µm. FlexImaging 4.1 (Build116) was used to drive flexControl 3.4 (Build 125) during the acquisition. Data were visualized using flexImaging software (Bruker Daltonics). Spectral processing was performed using flexAnalysis 3.4 (Build 76) and SCiLs Lab 2014b (version 2.02.5378) software. MSI data were exported to SCiLs Lab software for statistical analysis, with processing using default pipelines carrying out peak picking, baseline correction and total ion current normalization, to remove systematic artifacts affecting mass spectral intensity.   Tumor and benign regions were initially compared by intensity plots and principal component analysis (PCA). Following this each region of cancer vs benign were compared using Hypothesis tests (receiver operating characteristics, ROC) to determine subsets of significantly different peaks (p<0.05), ranked by their area-under-the-curve (AUC) values. Peptides with an AUC ≥ 0.7 between cancer and benign tissue were selected for further analysis. These were referred to the reference library of peptide IDs generated by LC-MALDI-MS/MS and were incorporated into combined lists from each tissue in the MSI experiment.      Reference peptide library  LC-MALDI analysis was performed to generate a reference library of peptides present in the antigen-retrieved, trypsin-digested tissue samples, to be subsequently matched to peptides of interest found in MSI experiments. MALDI-MS and MS/MS spectra were acquired on an UltrafleXtreme spectrometer using CHCA as matrix. A Thermo Ultimate 3000 nano-UPLC (Thermo Fisher) was coupled to a Bruker Proteineer fcII spotting robot (Bruker Daltonics) to deposit eluent onto 384 or 1536 sample AnchorChip MALDI target plates under conditions as described in Hunt NJ, Phillips L, et al. Proteomic MALDI-TOF/TOF-IMS examination of peptide expression in the formalin fixed brainstem and changes in sudden infant death syndrome infants. J Proteomics (2016) 138:48-60."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["MSI data were exported to SCiLs Lab software for statistical analysis, with processing using default pipelines carrying out peak picking, baseline correction and total ion current normalization, to remove systematic artifacts affecting mass spectral intensity. Tumor and benign regions were initially compared by intensity plots and principal component analysis (PCA). Following this each region of cancer vs benign were compared using Hypothesis tests (receiver operating characteristics, ROC) to determine subsets of significantly different peaks (p<0.05), ranked by their area-under-the-curve (AUC) values. Peptides with an AUC ≥ 0.7 between cancer and benign tissue were selected for further analysis. These were referred to the reference library of peptide IDs generated by LC-MALDI-MS/MS and were incorporated into combined lists from each tissue in the MSI experiment."],"omics_type":["Proteomics"],"labhead":["Robert Charles Baxter"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Hormones & Cancer Group, Kolling Institute, University of Sydney, Sydney 2065, Australia"],"species":["Homo Sapiens (human)"],"publication":["31139569 Phillips L, Gill AJ, Baxter RC. Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging. Front Oncol. 2019 9:379 10.3389/fonc.2019.00379"],"submitter_mail":["robert.baxter@sydney.edu.au"],"submitter_affiliation":["The University of Sydney"],"submitter_country":["Australia"],"pubmed_abstract":["There are no widely-accepted prognostic markers currently available to predict outcomes in patients with triple-negative breast cancer (TNBC), and no targeted therapies with confirmed benefit. We have used MALDI mass spectrometry imaging (MSI) of tryptic peptides to compare regions of cancer and benign tissue in 10 formalin-fixed, paraffin-embedded sections of TNBC tumors. Proteins were identified by reference to a peptide library constructed by LC-MALDI-MS/MS analyses of the same tissues. The prognostic significance of proteins that distinguished between cancer and benign regions was estimated by Kaplan-Meier analysis of their gene expression from public databases. Among peptides that distinguished between cancer and benign tissue in at least 3 tissues with a ROC area under the curve >0.7, 14 represented proteins identified from the reference library, including proteins not previously associated with breast cancer. Initial network analysis using the STRING database showed no obvious functional relationships except among collagen subunits COL1A1, COL1A2, and COL63A, but manual curation, including the addition of EGFR to the analysis, revealed a unique network connecting 10 of the 14 proteins. Kaplan-Meier survival analysis to examine the relationship between tumor expression of genes encoding the 14 proteins, and recurrence-free survival (RFS) in patients with basal-like TNBC showed that, compared to low expression, high expression of nine of the genes was associated with significantly worse RFS, most with hazard ratios >2. In contrast, in estrogen receptor-positive tumors, high expression of these genes showed only low, or no, association with worse RFS. These proteins are proposed as putative markers of RFS in TNBC, and some may also be considered as possible targets for future therapies."],"pubmed_title":["Novel Prognostic Markers in Triple-Negative Breast Cancer Discovered by MALDI-Mass Spectrometry Imaging."],"pubmed_authors":["Phillips Leo L, Gill Anthony J AJ, Baxter Robert C RC"],"name_synonyms":["triple-receptor negative breast cancer, ER Negative PR Negative HER2 Negative Breast Neoplasms, triple-negative breast cancer, Triple-Negative Breast Neoplasms, Breast Neoplasm, ER Negative PR Negative HER2 Negative Breast Cancer, Triple Negative Breast Cancer, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, Breast Neoplasms, Triple Negative Breast Neoplasm, triple-negative breast carcinoma, Breast Cancer, Triple-Negative Breast Neoplasm, Breast Cancers, Triple-Negative Breast Cancer, Triple-Negative Breast Cancers, Triple-Negative, Triple-Negative., ER-Negative PR-Negative HER2-Negative Breast Cancer, TNBC"],"pubmed_abstract_synonyms":["DER/faint little ball, triple-receptor negative breast cancer, malignant tumor of the breast, Formol, Kaplan-Meier Survival, Laser Desorption-Ionization Mass Spectrometry, Collagens, Materials, AA960264, determination, Breast Neoplasms, Synthetic Peptide, Elp-B1, der, Matrix Assisted Laser Desorption Ionization Mass Spectrometry, Elp-1, Receptors, CG8998, mammary neoplasm, Estrogen Receptor Type II, Human Mammary Neoplasms, Errb1, protein, Estra, dRoc2, Nuclear Receptor, Tumor, TNBC, PIG61, triple-negative breast cancer, Polypeptides, Kaplan-Meier Survival Curve, peptido, \"neoplasm of breast (disorder)\" EXACT [SNOMEDCT_2005_07_31:126926005], Method, Mov-13, epidermal growth factor-activated receptor activity, Associations, triple-negative breast carcinoma, Methanal, Parafilm, AI552599, cancer of the breast, Relapses, Analysis, Zyderm, d-egf-r, Surface Enhanced Laser Desorption Ionization Mass Spectrometry, BC, portion of tissue, Estimate, Mammary Neoplasms, malignant neoplasm of breast, me75, Gene Expressions, Collagen alpha2(I), peptides, Triple Negative Breast Cancer, Product-Limit Methods, Analyses, Survival Analyses, Breast Cancers, Random Peptide Libraries, Recurrences, Microfibril Collagen Hemostat, Tissue, Formaldehyd, SIDNA, Oxomethane, Human Mammary Carcinomas, MS-MALD, Mass Spectrometry, MALDI MS, proteins, Futurology, Synthetic Peptide Library, Estimated, D17Mit170, flb, T1, Matrix Assisted Laser Desorption Ionization, Kaplan Meier Analysis, Mov13, collagen, COLIA1, malignant neoplasm, cancer of breast, alpha2 Chain, Collagen Fleece, Therapies, 9030024J15Rik, COL1A2, D-EGFR, Malignancies, Collagen, mammary cancer, Breast Malignant Neoplasms, NISBD2, Tumors, DER1, Predictions and Projections, Therapy, alpha2(I)-Collagen, Relapse, Carcinoma, \"breast neoplasm\" EXACT [MTH:120], Elp, PLATEST, Wa5, l(2)09261, DEgfr, Triple-Negative Breast Cancer, Test, Product Limit Method, Laser Desorption Ionization Mass Spectrometry, Tl3, Tl2, CG10079, DmelCG8998, Spectroscopy, torpedo/egfr, Benign, Collagen Type I, wa2, Recrudescence, tissue portion, Triple-Negative, Genetic Materials, NOS, simple tissue, Cola1, Cola2, DMSIDNA, Malignant Neoplasm of Breast, Genetic Material, Carcinomas, egfr, BcDNA:AT21612, Estrogen Receptor Type I, Peptide Libraries, Triple-Negative Breast Neoplasms, BcDNA:RE61847, Cola-2, Cola-1, Kaplan-Meier Survival Curves, HD-33, El, ER Negative PR Negative HER2 Negative Breast Cancer, death rate, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, DER/EGFR, EGFR, EGfr, EgfR, AI325291, dEgfr, Benign Neoplasms, DER flb, Peptide Phage Display Library, \"mammary neoplasm\" RELATED [], Torpedo/Egfr, Estrogen Receptors, Treatments, Random Peptide, Malignant Neoplasms, ROC1b, Degfr, Col1a-2, Col1a-1, Kaplan Meier Survival Curve, CG16988, Patient, breast cancer, Material, DEGFR, roc1b, Breast Tumors, Triple-Negative Breast Neoplasm, l(2)57DEFa, l(2)05351, Breast Malignant Tumors, Collagen Felt, dEGFR, Cistron, Polypeptide, DmHD-33, anon-EST:Liang-2.35, other neoplasm, cancer, ER-Negative PR-Negative HER2-Negative Breast Cancer, Platelets, ROC1B, Estrogen Receptors Type I, primary breast cancer, Estrogen Receptor, D-Egf, MALDI-MS, CG5099, Peptide Library, C-erb, Neoplasms, Benign Neoplasm, Triple-Negative Breast Cancers, mor1, alpha-Collagen, Gene, Mammary Cancers, roc2, mENA, EK2-6, Malignant, Human, Breast Malignant Tumor, Microfibril, Curve, Estrogen Nuclear Receptor, Phage Display Library, Breast Tumor, Dermodress, Collastat, Survival, c-erbB, EGFr, Egfr, Estrogen Receptors Type II, Mass, Gene Products, \"mammary tumor\" EXACT [CSP2005:2016-0671], torpedo/Egfr, EGF receptor activity, breast tumor, Projections and Predictions, TOP, Random Peptide Library, Egf-r, Low, Type I, Mass Spectroscopy, Synthetic, network topology analysis, EGF-R, Human Mammary, Genetic, Malignancy, alpha-2 Type 1 Collagen, Mammary Neoplasm, Recrudescences, Estrogen Nuclear, NR3A1, Mammary Carcinoma, Avitene, top, Torpedo/DER, Treatments., Matrix Assisted, Kaplan-Meier, Expressions, alpha Collagen, Cancer of the Breast, top/flb, SELDI-TOF-MS, Neoplasias, Msi, ESR, Formalin, ROC2, l(2)57EFa, Malignant Tumor of Breast, time of survival, Clients, Mammary, Mammary Cancer, Triple Negative Breast Neoplasm, Kaplan Meier Test, peptidos, l(2)57Ea, Expression, Breast, mammary tumor, Collagenfleece, Survival Curve, MALD-MS, Cancer, Curves, Elp-B1RB1, Breast Carcinoma, Human Mammary Neoplasm, Kaplan Meier Survival Curves, Breast Carcinomas, clone 2.35, Malignant Neoplasm, cou, TGF-alpha receptor activity, ERBB, dEGFR1, Proteins, Product-Limit Method, Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry, Random, Survival Curves, Libraries, \"breast tumor\" EXACT [NCI2004_11_17:C2910], OI4, Cistrons, Client, DmelCG5099, Peptide, Breast Malignant Neoplasm, Product-Limit, Lr, MT, Roc, survival, native protein, epidermal growth factor receptor activity, DmelCG10079, Mammary Carcinomas, Protein, chemical analysis, Collagen Type 1 alpha-2, Neoplasm, Collagen Hemostat, Synthetic Peptide Libraries, Human Mammary Carcinoma, FORMALIN, DER/top, Library, Synthetic Peptide Combinatorial Library, Data Base, Pangen, Methods, Breast Neoplasm, primary cancer, Estrogen, top/DER, Matrix-Assisted, dRoc1b, other collagen, oim, survival analysis, Avicon, ERBB1, Cancers, Matrix-Assisted Laser Desorption-Ionization, wa-2, alpha 2(I) Collagen, malignant tumor, Phage Display Peptide Library, Methylene oxide, Protein Gene Products, alpha2 Type 1 Collagen, ER Negative PR Negative HER2 Negative Breast Neoplasms, Gene Proteins, Kaplan-Meier Test, Egf, MALDI, EFG-R, Therapeutic, Oxomethylene, Errp, Erbb, Breast Cancer, alpha 2 Collagen Type I, Estr, Der, DER, Bra, Treatment, Peptid, Kaplan-Meier Analysis, Cancer of Breast, transforming growth factor-alpha receptor activity, assay, Receptor, DmelCG16988, Type II, Future, Neoplasia, DER/torpedo, breast, HER1"],"data_synonyms":["Passive, CD203c, MPS2, NPP1, Laser Desorption-Ionization Mass Spectrometry, MALDI-MS, determination, Experiment., Neoplasms, Benign Neoplasm, Matrix Assisted Laser Desorption Ionization Mass Spectrometry, FBN, Computer, Tumor, Principal Component Analyses, Malignant, peptide, Polypeptides, peptido, ECTOL1, Mass, Software Engineering, Carrying, Analysis, Computer Program, WMS, Benson syndrome, Application, Mass Spectroscopy, Surface Enhanced Laser Desorption Ionization Mass Spectrometry, Npps, Passive Cutaneous, FLVCR, Open Source Softwares, portion of tissue, amyloidosis, SIDS, Pca-1, peptides, Malignancy, Analyses, Software Application, Open, biparietal Alzheimer disease, Tissue, Open Source Software, Computer Programs and Programming, MS-MALD, Mass Spectrometry, MALDI MS, twy, Artefacts, Matrix Assisted, lichen amyloidosis, Computer Software Application, OCTD, SELDI-TOF-MS, Neoplasias, Matrix Assisted Laser Desorption Ionization, Tools, malignant neoplasm, Artifact, TIC, site, MFSD7B, peptidos, Malignancies, GPHYSD2, statistical analysis, SGS, MALD-MS, Cancer, Tumors, Applications Software, Open Source, data, Computer Software, Malignant Neoplasm, Artefact, Pdnp1, familial, arteria cerebri communicans posterior, Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry, familial cutaneous lichen, Ids, Laser Desorption Ionization Mass Spectrometry, Source Softwares, Peptide, Software Tools, Tool, Cutaneous Anaphylaxis, Programs, ACMICD, Spectroscopy, polypeptide, Program, Computer Applications, M6S1, Software Tool, 4833416E15Rik, Benign, C76301, MT, AI428932, Computer Applications Software, chemical analysis, Pca, PCA, Computer Applications Softwares, Neoplasm, POSTERIOR, sequence, tissue portion, MFS1, simple tissue, Softwares, Software, AXPC1, Library, region, WMS2, PCS, primary cancer, Software Applications, Matrix-Assisted, Source Software, Engineering, choanal atresia, Anaphylaxis, Benign Neoplasms, MASS, Cancers, Matrix-Assisted Laser Desorption-Ionization, malignant tumor, primary structure of sequence macromolecule, Malignant Neoplasms, Computer Programs, Applications, Principal Component, MALDI, Applications Softwares, PCARP, SSKS, PC-1, Peptid, Polypeptide, assay, E-NPP1, ttw, other neoplasm, Ly-41, Neoplasia, hypothesis, Computer Software Applications"],"pubmed_title_synonyms":["triple-receptor negative breast cancer, Triple-Negative Breast Neoplasms, Breast Neoplasm, Laser Desorption-Ionization Mass Spectrometry, ER Negative PR Negative HER2 Negative Breast Cancer, MALDI-MS, Triple Negative Breast Cancer, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, Breast Neoplasms, Matrix-Assisted, Breast Cancers, Triple-Negative Breast Cancer, Triple-Negative Breast Cancers, Matrix Assisted Laser Desorption Ionization Mass Spectrometry, Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry, MS-MALD, Mass Spectrometry, MALDI MS, Matrix Assisted, Matrix-Assisted Laser Desorption-Ionization, Matrix-Assisted Laser Desorption-Ionization., Laser Desorption Ionization Mass Spectrometry, TNBC, SELDI-TOF-MS, Matrix Assisted Laser Desorption Ionization, Spectroscopy, ER Negative PR Negative HER2 Negative Breast Neoplasms, triple-negative breast cancer, MALDI, Triple Negative Breast Neoplasm, triple-negative breast carcinoma, Breast Cancer, Triple-Negative Breast Neoplasm, Mass, Triple-Negative, ER-Negative PR-Negative HER2-Negative Breast Cancer, Mass Spectroscopy, Surface Enhanced Laser Desorption Ionization Mass Spectrometry, MALD-MS"],"description_synonyms":["DER/faint little ball, triple-receptor negative breast cancer, malignant tumor of the breast, Formol, Laser Desorption-Ionization Mass Spectrometry, Collagens, Materials, AA960264, determination, Breast Neoplasms, Synthetic Peptide, Elp-B1, der, Matrix Assisted Laser Desorption Ionization Mass Spectrometry, Elp-1, Receptors, mammary neoplasm, Estrogen Receptor Type II, Human Mammary Neoplasms, Errb1, protein, Estra, Nuclear Receptor, Tumor, TNBC, PIG61, triple-negative breast cancer, Polypeptides, peptido, \"neoplasm of breast (disorder)\" EXACT [SNOMEDCT_2005_07_31:126926005], Mov-13, epidermal growth factor-activated receptor activity, Associations, triple-negative breast carcinoma, Methanal, Parafilm, AI552599, cancer of the breast, Relapses, Analysis, Zyderm, d-egf-r, Surface Enhanced Laser Desorption Ionization Mass Spectrometry, BC, portion of tissue, Mammary Neoplasms, malignant neoplasm of breast, me75, Gene Expressions, Collagen alpha2(I), peptides, Triple Negative Breast Cancer, Analyses, Survival Analyses, Breast Cancers, Random Peptide Libraries, Recurrences, Microfibril Collagen Hemostat, Tissue, Formaldehyd, Oxomethane, Human Mammary Carcinomas, MS-MALD, Mass Spectrometry, MALDI MS, proteins, Synthetic Peptide Library, Estimated, free, D17Mit170, flb, T1, Matrix Assisted Laser Desorption Ionization, Mov13, collagen, COLIA1, malignant neoplasm, cancer of breast, alpha2 Chain, Collagen Fleece, 9030024J15Rik, COL1A2, D-EGFR, Malignancies, Collagen, mammary cancer, Breast Malignant Neoplasms, NISBD2, Tumors, DER1, alpha2(I)-Collagen, Relapse, Carcinoma, \"breast neoplasm\" EXACT [MTH:120], Elp, PLATEST, Wa5, l(2)09261, DEgfr, Triple-Negative Breast Cancer, Laser Desorption Ionization Mass Spectrometry, Tl3, Tl2, CG10079, Spectroscopy, torpedo/egfr, Benign, Collagen Type I, wa2, Recrudescence, tissue portion, Triple-Negative, Genetic Materials, NOS, simple tissue, Cola1, Cola2, fixed, Malignant Neoplasm of Breast, Genetic Material, Carcinomas, egfr, Estrogen Receptor Type I, Peptide Libraries, Triple-Negative Breast Neoplasms, Cola-2, Cola-1, HD-33, El, ER Negative PR Negative HER2 Negative Breast Cancer, death rate, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, DER/EGFR, EGFR, EGfr, EgfR, AI325291, dEgfr, Benign Neoplasms, DER flb, Peptide Phage Display Library, \"mammary neoplasm\" RELATED [], Torpedo/Egfr, Estrogen Receptors, Random Peptide, Malignant Neoplasms, Degfr, Col1a-2, Col1a-1, Patient, breast cancer, Material, DEGFR, Breast Tumors, Triple-Negative Breast Neoplasm, l(2)57DEFa, l(2)05351, Breast Malignant Tumors, Collagen Felt, dEGFR, Cistron, Polypeptide, DmHD-33, other neoplasm, cancer, ER-Negative PR-Negative HER2-Negative Breast Cancer, Platelets, Estrogen Receptors Type I, primary breast cancer, Estrogen Receptor, D-Egf, MALDI-MS, Peptide Library, C-erb, Neoplasms, Benign Neoplasm, Triple-Negative Breast Cancers, mor1, alpha-Collagen, Gene, Mammary Cancers, mENA, EK2-6, Malignant, Human, Breast Malignant Tumor, Microfibril, Estrogen Nuclear Receptor, Phage Display Library, Breast Tumor, Dermodress, Collastat, Survival, c-erbB, EGFr, Egfr, Estrogen Receptors Type II, Mass, Gene Products, \"mammary tumor\" EXACT [CSP2005:2016-0671], torpedo/Egfr, EGF receptor activity, breast tumor, TOP, Random Peptide Library, Egf-r, Low, Type I, Mass Spectroscopy, Synthetic, network topology analysis, EGF-R, Human Mammary, Genetic, Malignancy, alpha-2 Type 1 Collagen, Mammary Neoplasm, Recrudescences, Estrogen Nuclear, NR3A1, Mammary Carcinoma, Avitene, top, Torpedo/DER, Matrix Assisted, Expressions, alpha Collagen, Cancer of the Breast, top/flb, SELDI-TOF-MS, Neoplasias, ESR, Formalin, l(2)57EFa, Malignant Tumor of Breast, time of survival, Clients, Mammary, Mammary Cancer, Triple Negative Breast Neoplasm, peptidos, l(2)57Ea, Expression, Breast, mammary tumor, Collagenfleece, MALD-MS, Cancer, Elp-B1RB1, Breast Carcinoma, Human Mammary Neoplasm, Breast Carcinomas, Malignant Neoplasm, cou, TGF-alpha receptor activity, ERBB, dEGFR1, Proteins, Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry, Random, Libraries, \"breast tumor\" EXACT [NCI2004_11_17:C2910], OI4, Cistrons, Client, Peptide, Breast Malignant Neoplasm, Lr, MT, survival, native protein, epidermal growth factor receptor activity, DmelCG10079, Mammary Carcinomas, Protein, chemical analysis, Collagen Type 1 alpha-2, Neoplasm, Collagen Hemostat, Synthetic Peptide Libraries, Human Mammary Carcinoma, FORMALIN, DER/top, Library, Synthetic Peptide Combinatorial Library, Data Base, Pangen, Breast Neoplasm, primary cancer, Estrogen, top/DER, Protein., Matrix-Assisted, other collagen, oim, survival analysis, Avicon, ERBB1, Cancers, Matrix-Assisted Laser Desorption-Ionization, wa-2, alpha 2(I) Collagen, malignant tumor, Phage Display Peptide Library, Methylene oxide, Protein Gene Products, alpha2 Type 1 Collagen, ER Negative PR Negative HER2 Negative Breast Neoplasms, Gene Proteins, Egf, MALDI, EFG-R, Oxomethylene, Errp, Erbb, Breast Cancer, alpha 2 Collagen Type I, Estr, Der, DER, Bra, Peptid, Cancer of Breast, assay, transforming growth factor-alpha receptor activity, Receptor, Type II, Neoplasia, DER/torpedo, breast, HER1"],"sample_synonyms":["Formol, Laser Desorption-Ionization Mass Spectrometry, Synthetic Peptide, FEZL, aneurysmal cyst of bone, Lasers, Tumor, Apaf-1, mg/ml, Bca, Polypeptides, Pathologist, protein polypeptide chains, Method, type I, Methanal, lamina pallidi incompleta, High Performance Liquid Chromatography, Antigen, AGM4, 4, Software Engineering, Analysis, 7, 9, placement, WMS, Benson syndrome, ASD2, aneurysmal bone cyst (disease), bca, ABC, amyloidosis, Grain, C79325, hac-1, Analyses, Surgical Pathology, Aneurysmal, Surface, Tissue, Oxomethane, MS-MALD, Hemotoxylin, Surface-Active, proteins, Artefacts, Synthetic Peptide Library, HPLC, AI047805, Matrix Assisted Laser Desorption Ionization, Dehydrated ethanol, anatomical tube, ACN, Acn, sample, Chromatography, n, TIC, CT, 10(6H)-pentol, High Speed Liquid, Histological Labeling, SGS, Tumors, spiritus vini, Infant Death, Ito, lamina medullaris accessoria, Pdnp1, acid, Ct, anon-53Fa, Liquid Chromatography, familial, arteria cerebri communicans posterior, l(2)SH0173, familial cutaneous lichen, Procedure, not genetically inherited, Software Tools, Absolute Alcohol, ACMICD, Computer Applications, 4833416E15Rik, Benign, Dm1, aneurysmal bone cyst, SATB2-associated syndrome, 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{(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol, choanal atresia, Truncus Cerebrus, Dark/Dapaf-1/HAC1, Benz(b)indeno(1, Cancers, Matrix-Assisted Laser Desorption-Ionization, malignant tumor, primary structure of sequence macromolecule, ME-IV, plan specification, Computer Programs, Gene Proteins, ZFP312, High Pressure, Applications Softwares, Oxomethylene, Amphiphilic Agents, ttw, biopsy, Neoplasia, formerly, hypothesis, Hac-1/Dark, Grain Alcohol, Brainstem, Meth, determination, DmelCG6829, Pa, Matrix Assisted Laser Desorption Ionization Mass Spectrometry, histology, Imaging, protein, Principal Component Analyses, 1-hydroxyethane, extracted material, alcohol, Truncus Cerebri, peptide, Cut, Ethanol, Techniques, peptido, BANF, l(1)7Ba, l(1)7Bb, Alkohol, Min, Apaf1, cytopathology, protein aggregate, ARK, Computer Program, DmelCG42273, Surface Enhanced Laser Desorption Ionization Mass Spectrometry, portion of tissue, 3-hydroxy-5-estrane-17-carbonitrile, 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Active Agents, dapaf-1, dapaf, dark, lichen amyloidosis, SELDI-TOF-MS, OCTD, Amphiphilic, DmelCG11387, DARK, Clients, Artifact, Ultra Performance Liquid Chromatography, site, dArk, Dapaf-1, FEZ, 2-iodo-, statistical analysis, TCEP, BLNK-S, High-Performance Liquid Chromatography, Applications Software, Peptidomics., Open Source, DYRK1, data, Computer Software, 2q32q33 microdeletion syndromes, Surfactant, protein complex, Continuous Wave Lasers, apaf1, brainstem, Client, Labeling, Peptide, light amplification by the stimulated emission of radiation, Cutaneous Anaphylaxis, Brain Stems, Software Tool, natural protein, AI428932, Protein, IMS, AI551343, sequence, FORMALIN, Dyrk1, Vacuums, Dark, (3alpha, Software, Dark/Apaf-I, truncus encephalicus, WMS2, Ethyl Alcohol, VSD1, SAS, 10^[-9], PRSS, Matrix-Assisted, Active Agents, CC1, Engineering, Tripcellim, patient, dApaf-1/DARK/HAC-1, Phage Display Peptide Library, Brainstems, sample population, Methylene oxide, Protein Gene Products, Trypure, Incontinentia pigmenti, hydroxyethane, HMI, MALDI, Pressures, concentration, PCARP, SSKS, Peptid, High Performance Liquid, assay, E-NPP1, SCH, IPA, dAPAF-1, 3-OHECN"],"additional_accession":[]},"is_claimable":false,"name":"Prognostic Markers in Triple-Negative Breast Cancer","description":"There are no widely-accepted prognostic markers currently available to predict outcomes in patients with triple-negative breast cancer (TNBC), and no targeted therapies with confirmed benefit. We have used MALDI mass spectrometry imaging (MSI) of tryptic peptides to compare regions of cancer and benign tissue in 10 formalin-fixed, paraffin-embedded sections of TNBC tumors. Proteins were identified by reference to a peptide library constructed by LC-MALDI-MS/MS analyses of the same tissues. The prognostic significance of proteins that distinguished between cancer and benign regions was estimated by Kaplan-Meier analysis of their gene expression from public databases. Among peptides that distinguished between cancer and benign tissue in at least 3 tissues with a ROC area under the curve >0.7, 14 represented proteins identified from the reference library, including proteins not previously associated with breast cancer.  Initial network analysis using the STRING database showed no obvious functional relationships except among collagen subunits COL1A1, COL1A2, and COL63A, but manual curation, including the addition of EGFR to the analysis, revealed a unique network connecting 10 of the 14 proteins. Kaplan-Meier survival analysis to examine the relationship between tumor expression of genes encoding the 14 proteins, and recurrence-free survival (RFS) in patients with basal-like TNBC showed that, compared to low expression, high expression of nine of the genes was associated with significantly worse RFS, most with hazard ratios >2. In contrast, in estrogen receptor-positive tumors, high expression of these genes showed only low, or no, association with worse RFS. These proteins are proposed as putative markers of RFS in TNBC, and some may also be considered as possible targets for future therapies.","dates":{"publication":"2019-05-06","submission":"2019-04-08"},"accession":"PXD013397","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:108018","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:2736291","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:294671","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:2767846","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:468822","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:342808","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:709964","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:156974","NEWT:3714","NCBITaxon:37162","NEWT:3715","NEWT:2065263","NEWT:199225","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:29022","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:1883426","NEWT:8165","NEWT:96794","NEWT:10401","NEWT:10886","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1955249","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:219809","NEWT:219808","NEWT:119562","NEWT:1883446","NEWT:31345","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:141469","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:291146","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:235455","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:911022","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:717989","NEWT:33952","NEWT:1255232","NEWT:11723","NEWT:445","NEWT:153009","NEWT:1004879","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:1871049","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:156981","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:219799","NEWT:219798","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:299467","NEWT:9541","NEWT:51350","NEWT:8694","NEWT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