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pmid:29861858
High expression of nucleoporin 133 mRNA in bone marrow CD138+ cells is a poor prognostic factor in multiple myeloma.
Soushi Ibata · Masayoshi Kobune · Shohei Kikuchi · Masahiro Yoshida · Shogo Miura · Hiroto Horiguchi · Kazuyuki Murase · Satoshi Iyama · Kohichi Takada · Koji Miyanishi · Junji Kato
Oncotarget · 2018 doi:10.18632/oncotarget.25350
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, the optimal therapeutic strategies to introduce these drugs for heterogeneous patients with multiple myeloma (MM) have not yet been clarified. In the present study, we attempted to identify a new factor indicating poor prognosis in CD138+ myeloma cells using accumulated Gene Expression Omnibus (GEO) datasets from studies of MM and to assess the relationship between gene expression and survival using MAQC-II Project Myeloma (GSE24080). Five GEO datasets (GSE5900, GSE58133, GSE68871, GSE57317 and GSE16791) which were analyzed by the same microarray platform (GLP570) were combined into one MM database including various types of MM. However, we found that gene expression levels were quite heterogeneous. Hence, we focused on the differentially-expressed genes (DEGs) between newly-diagnosed MM and relapsed/refractory MM and found that the expression levels of more than 20 genes changed two-fold or more. Additionally, pathway analysis indicated that six pathways including Hippo signaling were significantly enriched. Then, we applied all DEGs and genes associated with core enrichment for GSE24080 to evaluate their involvement in disease prognosis. We found that nucleoporin 133 (NUP133) is an independent poor prognostic factor by Cox proportional hazard analysis. These results suggested that high expression of NUP133 could be useful when choosing the appropriate MM therapy and may be a new target of MM therapy.", "claims": [{"id": "claim-method", "statement": "The relationship between DEGs and OS were evaluated using the publicly accessible MAQC-II Project MM dataset (GSE24080) from the GEO using the Cox proportional hazard model provided from EZR [26].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29861858", "locator": "sections[11] \"Statistical analysis\" paragraph 3", "quote": "The relationship between DEGs and OS were evaluated using the publicly accessible MAQC-II Project MM dataset (GSE24080) from the GEO using the Cox proportional hazard model provided from EZR [26]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To assess the relationship between candidate genes and survival, we used another dataset, The MicroArray Quality Control (MAQC)-II Project MM dataset (GSE24080) (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24080) [14]. In this dataset, gene expression profiling of highly-purified bone marrow plasma cells in NDMM (N = 559) was available. Moreover, this dataset was analyzed using an Affymetrix Human Genome U133 Plus 2.0 Array by which myeloma dataset #2 was also analyzed. Furthermore, supplementary data regarding clinical information such as survival time, the total number of deaths (N = 172), recurrence or progression (N = 249) and cytogenetic abnormalities of individual patients was included with this dataset. 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"2.797", "7.786", "65.50", "1.80E-191", "9.71E-191"], ["KLK7", "2.797", "5.373", "49.27", "2.16E-154", "2.44E-154"], ["MICALL2", "2.710", "7.799", "69.14", "1.01E-198", "8.87E-198"], ["LOC728190", "2.603", "5.970", "54.12", "2.11E-166", "3.88E-166"], ["LOC149773", "2.423", "4.810", "64.68", "8.59E-190", "4.30E-189"], ["SBNO2", "2.350", "5.761", "61.83", "8.02E-184", "3.51E-183"]], "row_count": 11, "column_count": 6, "numeric_cells": 55, "header_rows": 1, "locator": "section[4]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:29861858:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9043e2e3af1ff7e5228c3d62ecf5ca0dcef63a400d2be5a9f48f065f0b1e1699", "bytes": 639, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[2]#T2", "version": null, "note": "Summary of the results of GSEA analysis", "structure": {"pmcid": "PMC5982762", "section_index": 4, "section_title": "The results of DEGs and GSEA in RRMM", "row_count": 7, "column_count": 4}, "table": {"label": "Table 2", "caption": "Summary of the results of GSEA analysis", "rows": [["Pathway (REACTOME)", "SIZE", "NES", "NOM P-val"], ["1. SIGNALING_BY_HIPPO", "16", "1.5587571", "0.027290449"], ["2. REGULATION_OF_IFNA_SIGNALING", "24", "1.5417559", "0.025477707"], ["3. LIGAND_GATED_ION_CHANNEL_TRANSPORT", "20", "1.5310737", "0.014403292"], ["4. KERATAN_SULFATE_KERATIN_METABOLISM", "26", "1.5274918", "0.029045643"], ["5. KERATAN_SULFATE_ BIOSYNTHESIS", "22", "1.4906782", "0.04158004"], ["6. TRAF6_MEDIATED_IRF7_ACTIVATION", "27", "1.4500268", "0.04477612"]], "row_count": 7, "column_count": 4, "numeric_cells": 24, "header_rows": 1, "locator": "section[4]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:29861858:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:482ded56645bd90ff6012ae6b41b4d45a90b98122fe254a6c7226dc0dfe02c9c", "bytes": 2391, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#T3", "version": null, "note": "Univariate analysis of the relationship between gene expression and OS by Cox proportional hazard model using the publicly accessible MAQC-II Project MM dataset (GSE24080)", "structure": {"pmcid": "PMC5982762", "section_index": 5, "section_title": "Identification of a new poor prognostic factor in patients with MM", "row_count": 47, "column_count": 3}, "table": {"label": "Table 3", "caption": "Univariate analysis of the relationship between gene expression and OS by Cox proportional hazard model using the publicly accessible MAQC-II Project MM dataset (GSE24080)", "rows": [["Gene symbol", "Hazard ratio (95% CI)", "P value"], ["CSNK1A1P1", "1.118 (0.943–1.325)", "0.2001"], ["GABRA2", "0.934 (0.725–1.204)", "0.5977"], ["GABRA4", "1.048 (0.890–1.235)", "0.5715"], ["GABRA5", "1.037 (0.925–1.163)", "0.5300"], ["GABRB1", "0.975 (0.841–1.130)", "0.7314"], ["GABRG2", "1.242 (1.048–1.471)", "0.0125*"], ["GABRG3", "1.045 (0.830–1.315)", "0.7108"], ["GABRR1", "0.892 (0.726–1.095)", "0.2731"], ["GLRA1", "1.208 (1.011–1.444)", "0.0374*"], ["GLRA3", "0.985 (0.817–1.187)", "0.8699"], ["GLRB", "0.978 (0.800–1.194)", "0.8244"], ["IFNA1", "1.102 (0.973–1.249)", "0.1249"], ["IFNA4", "1.465 (1.076–1.997)", "0.0155*"], ["IFNA5", "0.909 (0.692–1.195)", "0.4947"], ["IFNA6", "0.953 (0.836–1.086)", "0.4658"], ["IFNA7", "0.971 (0.834–1.130)", "0.7016"], ["IFNA8", "0.996 (0.886–1.119)", "0.9459"], ["IFNA10", "1.120 (0.900–1.393)", "0.3097"], ["IFNA14", "0.894 (0.661–1.209)", "0.4677"], ["IFNA16", "0.758 (0.545–1.053)", "0.0986"], ["IFNA17", "0.876 (0.598–1.282)", "0.4946"], ["IRF2", "0.816 (0.597–1.114)", "0.1995"], ["KCTD7", "1.019 (0.770–1.347)", "0.8973"], ["KERA", "1.032 (0.834–1.276)", "0.7731"], ["KLK7", "1.059 (0.812–1.380)", "0.6744"], ["LATS1", "1.123 (0.872–1.445)", "0.3700"], ["LOC149773", "1.040 (0.820–1.320)", "0.7446"], ["LOC283432", "0.970 (0.878–1.072)", "0.5534"], ["LOC283587", "1.087 (0.976–1.211)", "0.1284"], ["LOC728190", "1.010 (0.709–1.438)", "0.9567"], ["LOC100287927", "0.794 (0.593–1.062)", "0.1204"], ["LOC100507880", "0.949 (0.786–1.146)", "0.5893"], ["LPCAT1", "0.931 (0.800–1.083)", "0.3523"], ["MICALL2", "0.850 (0.652–1.107)", "0.2270"], ["NUP133", "1.658 (1.150–2.392)", "0.0068*"], ["OGN", "1.139 (0.944–1.375)", "0.1734"], ["OMD", "1.139 (0.920–1.411)", "0.2325"], ["P2RY1", "0.920 (0.791–1.069)", "0.2753"], ["PATID", "0.999 (0.999–1.000)", "0.0581"], ["PKP1", "1.013 (0.784–1.310)", "0.9205"], ["SBNO2", "0.988 (0.811–1.204)", "0.9056"], ["STK4", "1.123 (0.764–1.650)", "0.5561"], ["TARBP2", "1.101 (0.708–1.712)", "0.6705"], ["XKR6", "0.859 (0.656–1.124)", "0.2679"], ["YAP1", "0.820 (0.621–1.083)", "0.1621"], ["ZNF677", "0.966 (0.778–1.199)", "0.7529"]], "row_count": 47, "column_count": 3, "numeric_cells": 105, "header_rows": 1, "locator": "section[5]/table-wrap[1]#T3"}}, {"id": "asset:table:pmid:29861858:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f195364499a3390372ecfb67584328985cc0e78a7548e1ca4a9ecbd6c86ad88a", "bytes": 416, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[2]#T4", "version": null, "note": "Multivariate analysis by the Cox proportional hazard model with stepwise regression using the Bayesian information criterion (BIC)", "structure": {"pmcid": "PMC5982762", "section_index": 5, "section_title": "Identification of a new poor prognostic factor in patients with MM", "row_count": 3, "column_count": 4}, "table": {"label": "Table 4", "caption": "Multivariate analysis by the Cox proportional hazard model with stepwise regression using the Bayesian information criterion (BIC)", "rows": [["Gene symbol", "Hazard ratio (95% CI)", "P-value"], ["NUP133", "1.55", "(1.14–2.09)", "4.7E-03"], ["Cyto.Abn", "2.15", "(1.58–2.92)", "9.1E-07"]], "row_count": 3, "column_count": 4, "numeric_cells": 8, "header_rows": 1, "locator": "section[5]/table-wrap[2]#T4"}}], "gaps": ["asset:data:geo:GSE24080 not downloaded", "asset:data:geo:GSE24080 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {"p_value": "n-Whitney U-test, and a P-value < 0"}, 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analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC analysis"}}, {"id": "method-6", "family": null, "specific": null, "label": "Cox proportional hazard model", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The relationship between DEGs and OS were evaluated using the publicly accessible MAQC-II Project MM dataset (GSE24080) from the GEO using the Cox proportional hazard model provided from EZR [26]."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE24080"], "resolved_accessions": ["GSE24080"], "statements": ["To assess the relationship between candidate genes and survival, we used another dataset, The MicroArray Quality Control (MAQC)-II Project MM dataset (GSE24080) (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24080) [14]. In this dataset, gene expression profiling of highly-purified bone marrow plasma cells in NDMM (N = 559) was available. Moreover, this dataset was analyzed using an Affymetrix Human Genome U133 Plus 2.0 Array by which myeloma dataset #2 was also analyzed. Furthermore, supplementary data regarding clinical information such as survival time, the total number of deaths (N = 172), recurrence or progression (N = 249) and cytogenetic abnormalities of individual patients was included with this dataset. After all data of GSE24080 were downloaded and combined with clinical information, the relationship between all candidate genes and OS was analyzed using the Cox proportional hazard model."], "basis": "The paper names GSE24080 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:29861858", "data:geo:GSE24080", "asset:table:pmid:29861858:1", "asset:table:pmid:29861858:2", "asset:table:pmid:29861858:3", "asset:table:pmid:29861858:4"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE24080"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:39Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 42847, "completion_tokens": 4195, "cached_tokens": 2088}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:29861858", "type": "paper", "label": "pmid:29861858"}, {"id": "source:pmid:29861858", "type": "manuscript", "label": "PMID 29861858 full text"}, {"id": "data:geo:GSE24080", "type": "dataset", "label": "GEO GSE24080"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29861858", "type": "paper", "label": "pmid:29861858"}, {"id": "source:pmid:29861858", "type": "manuscript", "label": "PMID 29861858 full text"}, {"id": "data:geo:GSE24080", "type": "dataset", "label": "GEO GSE24080"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29861858", "type": "extraction", "used": ["source:pmid:29861858"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE24080", "type": "accession_resolution", "used": ["data:geo:GSE24080"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:29861858", "parent_hash": "sha256:2ed2982d31565b5b83a3650e535aba2eda5d3a6eca02e13f6320dfcd598f854a", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE24080 licence not read", "asset:data:geo:GSE24080 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nd GSE16791) which were analyzed by the same microarray platform (GLP570) were combined into one MM", "s and survival, we used another dataset, The MicroArray Quality Control (MAQC)-II Project MM dataset", "ed with poor prognosis of NDMM. 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