Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29541007", "kind": "science-record", "revision": 6, "content_hash": "sha256:ece5c3d7fffbb3b62961508a7f18b14b7400f2dad09712db2483762c35885b2a", "created_at": "2026-11-01T15:40:32Z", "updated_at": "2026-11-01T21:21:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases.", "doi": "10.1186/s12014-018-9189-x", "pmid": "29541007", "authors": ["Nina Zila", "Andrea Bileck", "Besnik Muqaku", "Lukas Janker", "Ossia M Eichhoff", "Phil F Cheng", "Reinhard Dummer", "Mitchell P Levesque", "Christopher Gerner", "Verena Paulitschke"], "journal": "Clinical proteomics", "year": 2018, "abstract": "BACKGROUND: MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases.\nMETHODS: Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer. For further validation steps after bioinformatics analysis, a targeted LC-QQQ-MS approach, as well as Western blot, immunohistochemistry and immunocytochemistry was performed.\nRESULTS: In this pilot study, we were able to identify 5977 proteins by LC-MS analysis (data are available via ProteomeXchange with identifier PXD007592). Based on PFS, samples were classified into good responders (PFS ≥ 6 months) and poor responders (PFS [Formula: see text] 3 months). By evaluating these proteomic profiles according to gene ontology (GO) terms, KEGG pathways and gene set enrichment analysis (GSEA), we could characterize differences between the two distinct groups. We detected an EMT feature (up-regulation of N-cadherin) as classifier between the two groups, V-type proton ATPases, cell adhesion proteins and several transporter and exchanger proteins to be significantly up-regulated in poor responding patients, whereas good responders showed an immune activation, among other features. We identified class-discriminating proteins based on nearest shrunken centroids, validated and quantified this signature by a targeted approach and could correlate parts of this signature with resistance using the CPL/MUW proteome database and survival of patients by TCGA analysis. We further validated an EMT-like signature as a major discriminator between good and poor responders on primary melanoma cells derived from cerebral metastases. Higher immune activity is demonstrated in patients with good response to MAPKi by immunohistochemical staining of biopsy samples of cerebral melanoma metastases.\nCONCLUSIONS: Employing proteomic analysis, we confirmed known extra-cerebral resistance mechanisms in the cerebral metastases and further discovered possible brain specific mechanisms of drug efflux, which might serve as treatment targets or as predictive markers for these kinds of metastasis.", "claims": [{"id": "claim-method", "statement": "To identify a potential biomarker profile, a classifier based on nearest shrunken centroids was constructed using ClaNC and R [43]. Priors were chosen according to the number of samples. The performance of the classifier was tested by leaving-one-out cross validation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29541007", "locator": "sections[5] \"LC–MS shotgun data analysis\" paragraph 2", "quote": "To identify a potential biomarker profile, a classifier based on nearest shrunken centroids was constructed using ClaNC and R [43]. Priors were chosen according to the number of samples. The performance of the classifier was tested by leaving-one-out cross validation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD007592 and https://doi.org/10.6019/pxd007592.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29541007", "locator": "sections[31] \"Availability of data and material\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD007592 and https://doi.org/10.6019/pxd007592."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used a nearest-shrunken-centroids classifier to identify discriminative proteins, and the underlying LC–MS proteomics source data were made available through ProteomeXchange under identifier PXD007592.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29541007", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified class-discriminating proteins based on nearest shrunken centroids, validated and quantified this signature by a targeted approach and could correlate parts of this signature with resistance using the CPL/MUW proteome database and survival of patients by TCGA analysis."}, {"asset": "source:pmid:29541007", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In this pilot study, we were able to identify 5977 proteins by LC–MS analysis (data are available via ProteomeXchange with identifier PXD007592)."}, {"asset": "source:pmid:29541007", "locator": "sections[17] \"Identification of discriminative proteins\" paragraph 2", "quote": "To generalize our proteomic findings and enable the translation of the results towards clinical application, we constructed a classifier based on nearest shrunken centroids to identify a potential biomarker profile."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper used a nearest-shrunken-centroids classifier to identify discriminative proteins, and the underlying LC–MS proteomics source data were made available through ProteomeXchange under identifier PXD007592.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29541007"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD007592"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD007592"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29541007", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12014-018-9189-x", "sha256": "sha256:f62a81b8303c459ffbebda6170703a4fa3852551d3ff8d10dee783357a6ff5e2", "bytes": 79206, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12014-018-9189-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5844114", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD007592", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD007592", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD007592", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD007592 and https://doi.org/10.6019/pxd007592.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD007592 and https://doi.org/10.6019/pxd007592.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29541007:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:98cdeee604786d1a96eed6c0485f2a3576c0c8d53ee8171cb5ca44b0dff046b7", "bytes": 7155, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab1", "version": null, "note": "Proteins significantly up-regulated in poor responder patients as indicated in the volcano plot", "structure": {"pmcid": "PMC5844114", "section_index": 16, "section_title": "Functional discrimination of the subgroups", "row_count": 86, "column_count": 6}, "table": {"label": "Table 1", "caption": "Proteins significantly up-regulated in poor responder patients as indicated in the volcano plot", "rows": [["Acc. Nr.", "Protein name", "Gene name", "log2 fold change (t-test difference)", "p value", "t-test significant"], ["Eukaryotic translation initiation factors (EIFs)"], ["Q14232", "Translation initiation factor eIF-2B subunit alpha", "EIF2B1", "1.04", "2.48E − 03", ""], ["Q14152", "Eukaryotic translation initiation factor 3 subunit A", "EIF3A", "1.13", "5.71E − 03", ""], ["P55884", "Eukaryotic translation initiation factor 3 subunit B", "EIF3B", "1.57", "3.62E − 03", ""], ["O00303", "Eukaryotic translation initiation factor 3 subunit F", "EIF3F", "1.23", "9.41E − 03", ""], ["O75821", "Eukaryotic translation initiation factor 3 subunit G", "EIF3G", "1.59", "4.81E − 02", ""], ["Q13347", "Eukaryotic translation initiation factor 3 subunit I", "EIF3I", "2.88", "4.29E − 05", "*"], ["Q9UBQ5", "Eukaryotic translation initiation factor 3 subunit K", "EIF3 K", "1.85", "3.50E − 05", ""], ["Q9Y262", "Eukaryotic translation initiation factor 3 subunit L", "EIF3L", "1.57", "7.30E − 03", ""], ["P23588", "Eukaryotic translation initiation factor 4B", "EIF4B", "1.69", "1.44E − 03", ""], ["Q15056", "Eukaryotic translation initiation factor 4H", "EIF4H", "1.68", "3.92E − 04", ""], ["O60841", "Eukaryotic translation initiation factor 5B", "EIF5B", "1.26", "2.53E − 02", ""], ["Neuronal proteins"], ["Q8N111", "Cell cycle exit and neuronal differentiation protein 1", "CEND1", "2.86", "1.98E − 03", ""], ["P51674", "Neuronal membrane glycoprotein M6-a", "GPM6A", "5.30", "5.24E − 05", "*"], ["P62166", "Neuronal calcium sensor 1", "NCS1", "3.55", "6.65E − 05", "*"], ["Q7Z3B1", "Neuronal growth regulator 1", "NEGR1", "3.71", "1.93E − 03", ""], ["Q15818", "Neuronal pentraxin-1", "NPTX1", "3.07", "4.79E − 03", ""], ["Q92823", "Neuronal cell adhesion molecule", "NRCAM", "2.44", "3.48E − 03", ""], ["Q9UH03", "Neuronal-specific septin-3", "SEPT3", "3.40", "3.68E − 04", ""], ["P17600", "Synapsin-1", "SYN1", "4.68", "2.47E − 04", "*"], ["Q92777", "Synapsin-2", "SYN2", "5.49", "3.17E − 04", "*"], ["O14994", "Synapsin-3", "SYN3", "2.46", "5.70E − 03", ""], ["Transporter proteins"], ["P30531", "Sodium- and chloride-dependent GABA transporter 1", "SLC6A1", "3.44", "8.85E − 06", "*"], ["P43003", "Excitatory amino acid transporter 1", "SLC1A3", "3.17", "2.51E − 03", ""], ["P43004", "Excitatory amino acid transporter 2", "SLC1A2", "4.98", "5.16E − 03", ""], ["P43007", "Neutral amino acid transporter A", "SLC1A4", "1.81", "4.10E − 02", ""], ["P48066", "Sodium- and chloride-dependent GABA transporter 3", "SLC6A11", "2.12", "4.95E − 04", ""], ["Q15043", "Zinc transporter ZIP14", "SLC39A14", "1.28", "3.30E − 03", ""], ["Q6PML9", "Zinc transporter 9", "SLC30A9", "1.57", "1.36E − 02", ""], ["Q8N4V1", "Membrane magnesium transporter 1", "MMGT1", "1.19", "3.22E − 02", ""], ["Q8TBB6", "Probable cationic amino acid transporter", "SLC7A14", "1.78", "6.86E − 03", ""], ["Q96QE2", "Proton myo-inositol cotransporter", "SLC2A13", "2.68", "1.94E − 06", "*"], ["Q99726", "Zinc transporter 3", "SLC30A3", "2.03", "2.95E − 02", ""], ["Q9H1V8", "Sodium-dependent neutral amino acid transporter SLC6A17", "SLC6A17", "2.51", "1.39E − 02", ""], ["Q9NS82", "Asc-type amino acid transporter 1", "SLC7A10", "1.44", "6.39E − 03", ""], ["Exchanger proteins"], ["P32418", "Sodium/calcium exchanger 1", "SLC8A1", "1.66", "4.06E − 02", ""], ["Q8TCU6", "Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein", "PREX1", "1.03", "1.03E − 03", ""], ["Q92581", "Sodium/hydrogen exchanger 6", "SLC9A6", "1.76", "9.73E − 03", ""], ["Q9UPR5", "Sodium/calcium exchanger 2", "SLC8A2", "4.39", "1.18E − 03", ""], ["V-type proton ATPases"], ["Q15904", "V-type proton ATPase subunit S1", "ATP6AP1", "1.41", "3.12E − 02", ""], ["Q93050", "V-type proton ATPase 116 kDa subunit a isoform 1", "ATP6V0A1", "2.57", "2.75E − 04", ""], ["P27449", "V-type proton ATPase 16 kDa proteolipid subunit", "ATP6V0C", "2.36", "5.37E − 03", ""], ["P61421", "V-type proton ATPase subunit d 1", "ATP6V0D1", "3.96", "8.92E − 07", "*"], ["P38606", "V-type proton ATPase catalytic subunit A", "ATP6V1A", "1.82", "6.37E − 05", ""], ["P21281", "V-type proton ATPase subunit B, brain isoform", "ATP6V1B2", "1.62", "2.37E − 04", ""], ["P21283", "V-type proton ATPase subunit C 1", "ATP6V1C1", "1.51", "5.27E − 05", ""], ["Q9Y5K8", "V-type proton ATPase subunit D", "ATP6V1D", "2.19", "5.15E − 04", ""], ["P36543", "V-type proton ATPase subunit E 1", "ATP6V1E1", "1.27", "6.60E − 04", ""], ["Q16864", "V-type proton ATPase subunit F", "ATP6V1F", "3.12", "5.47E − 07", "*"], ["O75348", "V-type proton ATPase subunit G 1", "ATP6V1G1", "2.39", "5.16E − 04", ""], ["O95670", "V-type proton ATPase subunit G 2", "ATP6V1G2", "1.40", "4.11E − 04", ""], ["Q9UI12", "V-type proton ATPase subunit H", "ATP6V1H", "2.75", "4.83E − 04", ""], ["MAP-kinases"], ["P28482", "Mitogen-activated protein kinase 1", "MAPK1", "1.78", "6.70E − 04", ""], ["P53779", "Mitogen-activated protein kinase 10", "MAPK10", "2.27", "1.27E − 03", ""], ["P27361", "Mitogen-activated protein kinase 3", "MAPK3", "1.79", "1.39E − 03", ""], ["Q9UPT6", "C-Jun-amino-terminal kinase-interacting protein 3", "MAPK8IP3", "2.21", "1.83E − 03", ""], ["Cell adhesion proteins"], ["O00533", "Neural cell adhesion molecule L1-like protein", "CHL1", "1.59", "3.85E − 02", ""], ["O15394", "Neural cell adhesion molecule 2", "NCAM2", "2.56", "1.84E − 02", ""], ["P13591", "Neural cell adhesion molecule 1", "NCAM1", "3.72", "1.12E − 04", "*"], ["P32004", "Neural cell adhesion molecule L1", "L1CAM", "4.27", "1.91E − 06", "*"], ["Q14982", "Opioid-binding protein/cell adhesion molecule", "OPCML", "4.53", "7.99E − 04", "*"], ["Q14CZ8", "Hepatocyte cell adhesion molecule", "HEPACAM", "2.49", "1.23E − 02", ""], ["Q8N3J6", "Cell adhesion molecule 2", "CADM2", "4.32", "1.24E − 03", ""], ["Q8NFZ8", "Cell adhesion molecule 4", "CADM4", "1.74", "2.53E − 02", ""], ["Q92823", "Neuronal cell adhesion molecule", "NRCAM", "2.44", "3.48E − 03", ""], ["Calcium-ion binding proteins"], ["P62158", "Calmodulin", "CALM1", "1.36", "9.22E − 06", ""], ["Q14012", "Calcium/calmodulin-dependent protein kinase type 1", "CAMK1", "2.17", "4.56E − 04", ""], ["Q9UQM7", "Calcium/calmodulin-dependent protein kinase type II subunit alpha", "CAMK2A", "3.00", "5.85E − 04", ""], ["Q13554", "Calcium/calmodulin-dependent protein kinase type II subunit beta", "CAMK2B", "3.98", "2.08E − 03", ""], ["Q13555", "Calcium/calmodulin-dependent protein kinase type II subunit gamma", "CAMK2G", "2.77", "5.24E − 03", ""], ["Q16566", "Calcium/calmodulin-dependent protein kinase type IV", "CAMK4", "1.98", "1.25E − 02", ""], ["Q8N5S9", "Calcium/calmodulin-dependent protein kinase kinase 1", "CAMKK1", "2.13", "8.09E − 03", ""], ["Q96RR4", "Calcium/calmodulin-dependent protein kinase kinase 2", "CAMKK2", "2.03", "8.67E − 03", ""], ["Q9P1Y5", "Calmodulin-regulated spectrin-associated protein 3", "CAMSAP3", "2.35", "8.13E − 03", ""], ["P54750", "Calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase 1A", "PDE1A", "1.97", "5.00E − 03", ""], ["Q01064", "Calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase 1B", "PDE1B", "2.54", "1.25E − 02", ""], ["EMT"], ["P19022", "Cadherin-2", "CDH2", "2.53", "1.02E − 03", ""]], "row_count": 86, "column_count": 6, "numeric_cells": 277, "header_rows": 1, "locator": "section[16]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:29541007:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3364b96bb8beb44a8da39939d6af356a3e8e6b383a1f3a6306d46906a9fc2b9c", "bytes": 3146, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[2]#Tab2", "version": null, "note": "Proteins significantly up-regulated in good responder patients as indicated in the volcano plot", "structure": {"pmcid": "PMC5844114", "section_index": 16, "section_title": "Functional discrimination of the subgroups", "row_count": 39, "column_count": 6}, "table": {"label": "Table 2", "caption": "Proteins significantly up-regulated in good responder patients as indicated in the volcano plot", "rows": [["Acc. Nr.", "Protein name", "Gene name", "log2 fold change (t-test difference)", "p value", "t-test significant"], ["Immune response related proteins"], ["P05164", "Myeloperoxidase", "MPO", "4.53", "1.69E − 05", "*"], ["P01909", "HLA class II histocompatibility antigen, DQ alpha 1 chain", "HLA-DQA1", "1.43", "1.01E − 03", ""], ["P04233", "HLA class II histocompatibility antigen gamma chain", "CD74", "1.74", "7.47E − 03", ""], ["P20039", "HLA class II histocompatibility antigen, DRB1-11 beta chain", "HLA-DRB1", "2.99", "2.46E − 03", ""], ["Q95365", "HLA class I histocompatibility antigen, B-38 alpha chain", "HLA-B", "1.84", "3.64E − 03", ""], ["Q5Y7A7", "HLA class II histocompatibility antigen, DRB1-13 beta chain", "HLA-DRB1", "1.38", "1.70E − 03", ""], ["P01594", "Ig kappa chain V-I region AU", "", "1.07", "7.46E − 03", ""], ["P01609", "Ig kappa chain V-I region Scw", "", "1.58", "2.02E − 03", ""], ["P01613", "Ig kappa chain V-I region Ni", "", "1.86", "1.68E − 02", ""], ["P01617", "Ig kappa chain V-II region TEW", "", "1.61", "4.60E − 03", ""], ["P01623", "Ig kappa chain V-III region WOL", "", "1.89", "1.87E − 03", ""], ["P01777", "Ig heavy chain V-III region TEI", "", "1.78", "1.97E − 03", ""], ["P01767", "Ig heavy chain V-III region BUT", "", "1.46", "3.39E − 02", ""], ["P01779", "Ig heavy chain V-III region TUR", "", "2.24", "9.82E − 04", ""], ["P01834", "Ig kappa chain C region", "IGKC", "1.56", "4.17E − 03", ""], ["P01857", "Ig gamma-1 chain C region", "IGHG1", "1.40", "9.49E − 03", ""], ["P01860", "Ig gamma-3 chain C region", "IGHG3", "1.42", "1.01E − 02", ""], ["P01871", "Ig mu chain C region", "IGHM", "2.24", "7.25E − 03", ""], ["P01876", "Ig alpha-1 chain C region", "IGHA1", "1.12", "5.26E − 02", ""], ["P01880", "Ig delta chain C region", "IGHD", "1.36", "4.04E − 02", ""], ["Apolipoproteins"], ["O14791", "Apolipoprotein L1", "APOL1", "1.82", "1.43E − 03", ""], ["P02647", "Apolipoprotein A-I", "APOA1", "1.94", "2.86E − 04", ""], ["P04114", "Apolipoprotein B-100", "APOB", "3.55", "1.17E − 03", ""], ["P06727", "Apolipoprotein A-IV", "APOA4", "5.06", "2.61E − 06", "*"], ["Cell adhesion (in immune response)"], ["P16284", "Platelet endothelial cell adhesion molecule", "PECAM1", "1.48", "5.04E − 02", ""], ["P31997", "Carcinoembryonic antigen-related cell adhesion molecule 8", "CEACAM8", "1.86", "3.08E − 03", ""], ["P40199", "Carcinoembryonic antigen-related cell adhesion molecule 6", "CEACAM6", "1.16", "3.99E − 02", ""], ["Extracellular matrix (ECM) components"], ["P02452", "Collagen alpha-1(I) chain", "COL1A1", "3.67", "2.18E − 02", ""], ["P02751", "Fibronectin", "FN1", "2.61", "4.26E − 03", ""], ["P08123", "Collagen alpha-2(I) chain", "COL1A2", "3.24", "1.25E − 02", ""], ["P25067", "Collagen alpha-2(VIII) chain", "COL8A2", "1.29", "9.84E − 03", ""], ["P39059", "Collagen alpha-1(XV) chain", "COL15A1", "1.48", "4.46E − 02", ""], ["Q05707", "Collagen alpha-1(XIV) chain", "COL14A1", "2.53", "5.55E − 02", ""], ["Q96P44", "Collagen alpha-1(XXI) chain", "COL21A1", "1.78", "3.42E − 02", ""]], "row_count": 39, "column_count": 6, "numeric_cells": 121, "header_rows": 1, "locator": "section[16]/table-wrap[2]#Tab2"}}, {"id": "asset:table:pmid:29541007:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7ef1ee85a3f72714a45e0c2812388f54d449eb4d7c9ee650fda8af7cc14f9dc1", "bytes": 3521, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#Tab3", "version": null, "note": "Classification to nearest shrunken centroids for identification of the most class-discriminating proteins", "structure": {"pmcid": "PMC5844114", "section_index": 17, "section_title": "Identification of discriminative proteins", "row_count": 10, "column_count": 7}, "table": {"label": "Table 3", "caption": "Classification to nearest shrunken centroids for identification of the most class-discriminating proteins", "rows": [["Acc. Nr.", "Protein name", "Gene name", "log2 fold change (t-test difference)upregulated in poor responder", "p value", "t-test significant", "Functional role"], ["P21266", "Glutathione S-transferase Mu 3", "GSTM3", "2.68", "7.13E − 07", "*", "Uptake and detoxification of endogenous compounds and xenobiotics at the blood brain barrier [80]; many anticancer drugs are substrates for GST and, therefore, overexpression of GST is responsible for resistance to anti-cancer drugs in tumor cell lines [81]"], ["P61962", "DDB1- and CUL4-associated factor 7", "DCAF7", "2.06", "1.11E − 07", "*", "Substrate receptor for a ubiquitin-protein ligase complex; involved in the pathway protein ubiquitination; involved in normal and disease skin development [82]; has been shown to function as a scaffold protein for protein complexes involved in kinase signalling [83]"], ["P62937", "Peptidyl-prolyl cis–trans isomerase A", "PPIA", "0.75", "4.98E − 07", "", "Upregulated in resistant human breast cancer cell line (vs. sensitive cell line) [84]; PPIases accelerate the folding of proteins; catalyzes the cis–trans isomerization of proline imidic peptide bonds in oligopeptides [85]"], ["Q16864", "V-type proton ATPase subunit F", "ATP6V1F", "3.12", "5.47E − 07", "*", "V-ATPases are responsible for acidifying intracellular compartments [86]; an acidic environment leads to inactivation of T cells [56, 57]; supports the hypothesis that resistance is caused by the tumor inactivating immune cells"], ["Q6FI81", "Anamorsin", "CIAPIN1", "2.46", "2.38E − 05", "", "Anti-apoptotic effects in the cell; involved in negative control of cell death upon cytokine withdrawal [87]; may participate in breast cancer multi drug resistance (MDR) by regulating MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic capability of cells [88]"], ["Q6UWP2", "Dehydrogenase/reductase SDR family member 11", "DHRS11", "2.10", "1.64E − 07", "*", "Involved in estrogen biosynthesis, which is part of steroid biosynthesis [89]; proposed role in sex hormone, neurosteroid, androgen, estrogen and bile acid metabolism; mRNA highly expressed in testis, small intestine, colon, kidney and cancer cell lines [90]"], ["Q7Z7E8", "Ubiquitin-conjugating enzyme E2 Q1", "UBE2Q1", "1.80", "3.14E − 05", "", "Catalyzes the covalent attachment of ubiquitin to other proteins [91]; may function as an oncogene that induces proliferation of cancer cells, and could be a novel diagnostic tool and a potential therapeutic target for colorectal cancer (CRC) [92]"], ["Q8IVD9", "NudC domain-containing protein 3", "NUDCD3", "2.42", "2.78E − 05", "", "Interacts selectively and non-covalently with an unfolded protein; functions to maintain the stability of dynein intermediate chain [93]; depletion of this gene product results in aggregation and degradation of dynein intermediate chain, mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles, and loss of gamma-tubulin from spindle poles [94]"], ["Q8N4Q0", "Prostaglandin reductase 3", "ZADH2", "2.48", "2.44E − 06", "*", "Negatively modulates adipogenesis through regulation of PPARγ activity [95]; knockdown of prostaglandin reductase 1 (PTGR1) suppresses prostate cancer cell proliferation by inducing cell cycle arrest and apoptosis [96]"]], "row_count": 10, "column_count": 7, "numeric_cells": 38, "header_rows": 1, "locator": "section[17]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:PXD007592 not downloaded", "asset:data:geo:PXD007592 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-meier"}}, {"id": "method-2", "family": null, "specific": null, "label": "Nearest shrunken centroids classifier, tested by leaving-one-out cross-validation", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To identify a potential biomarker profile, a classifier based on nearest shrunken centroids was constructed using ClaNC and R [43]. 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