Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27903973", "kind": "science-record", "revision": 8, "content_hash": "sha256:f88b667a487bc5e48175682acab842bf638756ae045303519b374c10a83af255", "created_at": "2026-11-01T15:40:21Z", "updated_at": "2026-11-01T21:59:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.", "doi": "10.18632/oncotarget.13650", "pmid": "27903973", "authors": ["Han Yan", "Lu Wen", "Dan Tan", "Pan Xie", "Feng-Mei Pang", "Hong-Hao Zhou", "Wei Zhang", "Zhao-Qian Liu", "Jie Tang", "Xi Li", "Xiao-Ping Chen"], "journal": "Oncotarget", "year": 2017, "abstract": "The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.", "claims": [{"id": "claim-method", "statement": "Linear-regression analysis was performed to identify probes correlated with cytarabine IC50 in 96 blood cancer cell lines. Probes with P<0.05 were then selected for analysis in the GSE12417 dataset. Multivariate cox regression analysis (including age) was conducted to confirm whether the probes affect OS of CN-AML patients. Probes exhibited significance (p<0.05) in both the linear-regression analysis and the cox regression analysis in the same direction were screened.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27903973", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Linear-regression analysis was performed to identify probes correlated with cytarabine IC50 in 96 blood cancer cell lines. Probes with P<0.05 were then selected for analysis in the GSE12417 dataset. Multivariate cox regression analysis (including age) was conducted to confirm whether the probes affect OS of CN-AML patients. Probes exhibited significance (p<0.05) in both the linear-regression analysis and the cox regression analysis in the same direction were screened."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Based on GDSC release 5.0, 96 blood cancer cell lines with both natural log transformed IC50 values of cytarabine and normalized whole genome mRNA expression levels were selected in our study (Supplementary Table S1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27903973", "locator": "sections[11] \"GDSC cell lines\" paragraph 2", "quote": "Based on GDSC release 5.0, 96 blood cancer cell lines with both natural log transformed IC50 values of cytarabine and normalized whole genome mRNA expression levels were selected in our study (Supplementary Table S1)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using linear-regression and Cox regression analyses of cytarabine-response and AML survival data, the study derived a 42-probe chemo-sensitivity score that predicted poor outcomes in CN-AML and was validated in TCGA.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The scores were associated with OS in both the training sample (p=5.13 × 10−4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus."}, "evidence": [{"asset": "source:pmid:27903973", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established."}, {"asset": "source:pmid:27903973", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The scores were associated with OS in both the training sample (p=5.13 × 10−4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus."}, {"asset": "source:pmid:27903973", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779)."}, {"asset": "source:pmid:27903973", "locator": "sections[1] \"INTRODUCTION\" paragraph 5", "quote": "To find out whether genes correlated with chemo-sensitivity could also predict the outcome of AML, we downloaded IC50 values of cytarabine from 96 leukemia cell lines and raw whole genome expression data of these cell lines from GDSC in this study."}, {"asset": "source:pmid:27903973", "locator": "sections[1] \"INTRODUCTION\" paragraph 5", "quote": "Probes significantly associated with IC50 levels in the cells and OS in GSE12417 dataset, a whole genome expression dataset for CN-AML in NCBI Gene Expression Omnibus (GEO), were selected."}, {"asset": "source:pmid:27903973", "locator": "sections[1] \"INTRODUCTION\" paragraph 5", "quote": "Based on the selected probes, chemo-sensitivity score was derived and replicated in a TCGA CN-AML dataset."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using linear-regression and Cox regression analyses of cytarabine-response and AML survival data, the study derived a 42-probe chemo-sensitivity score that predicted poor outcomes in CN-AML and was validated in TCGA.", "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:27903973"], "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. 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Blood cancer cell lines", "GSE12417", "Prognostic Index"], ["p value", "t value", "U133AB sample", "U133 Plus sample"], ["p value", "Z value", "p value", "Z value"], ["ULK1", "209333_at", "1.44E-05", "−4.578", "0.045", "−2.004", "0.018", "−2.362", "−0.309"], ["PIGF", "205078_at", "2.54E-05", "4.431", "0.043", "2.020", "0.041", "2.045", "0.193"], ["ABCC5", "209380_s_at", "9.26E-05", "−4.085", "0.011", "−2.541", "0.035", "−2.109", "−0.336"], ["MRPL40", "203152_at", "9.84E-05", "4.069", "0.003", "2.959", "0.018", "2.366", "0.253"], ["DARS2", "218365_s_at", "1.60E-04", "3.934", "0.046", "1.992", "0.011", "2.532", "0.193"], ["ITSN1", "35776_at", "2.27E-04", "−3.835", "0.027", "−2.208", "0.041", "−2.041", "−0.274"], ["ZC3HAV1", "213051_at", "4.09E-04", "−3.665", "0.032", "−2.149", "0.017", "−2.397", "−0.355"], ["NDUFB5", "203621_at", "5.32E-04", "3.588", "0.003", "3.022", "0.004", "2.865", "0.341"], ["SKAP2", "204361_s_at", "7.54E-04", "3.483", "0.025", "2.243", "0.038", "2.072", "0.186"], ["ZNF451", "215012_at", "0.001", "−3.367", "0.038", "−2.070", "0.005", "−2.821", "−0.316"], ["IARS2", "217900_at", "0.002", "3.197", "0.010", "2.562", "0.018", "2.358", "0.212"], ["MPP1", "202974_at", "0.003", "−3.049", "0.018", "−2.367", "0.044", "−2.010", "−0.363"], ["ZNF259P1/ZPR1", "217185_s_at", "0.004", "2.961", "0.003", "3.023", "0.011", "2.541", "0.231"], ["BCL2L1", "212312_at", "0.004", "−2.916", "0.022", "−2.288", "0.042", "−2.032", "−0.309"], ["CHMP4A/TM9SF1", "218572_at", "0.006", "2.836", "0.026", "2.219", "0.047", "1.987", "0.197"], ["GAS2", "205848_at", "0.007", "2.744", "0.029", "2.185", "0.001", "3.403", "0.191"], ["ME2", "210154_at", "0.008", "2.715", "0.021", "2.307", "0.016", "2.412", "0.221"], ["ALCAM", "201951_at", "0.008", "2.710", "0.000", "3.634", "0.000", "5.064", "0.363"], ["DNAJC1", "218409_s_at", "0.009", "2.675", "0.005", "2.791", "0.023", "2.282", "0.259"], ["VDAC1", "212038_s_at", "0.009", "2.673", "0.005", "2.804", "0.018", "2.376", "0.213"], 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"section_title": "Validation of the association between 42-probe-based chemo-sensitivity score and survival in TCGA CN-AML patients", "row_count": 9, "column_count": 6}, "table": {"label": "Table 3", "caption": "Comparison of chemo-sensitivity score between genotypes of well-known somatic mutations affecting AML outcome", "rows": [["Mutation", "Wild type", "Mutation", "p value"], ["Score (Mean±SD)", "N", "Score (Mean±SD)", "N", ""], ["CEBPA", "0.612±3.561", "48", "−2.557±3.428", "5", "0.063"], ["DNMT3A R882", "−0.109±3.396", "42", "1.926±4.239", "11", "0.099"], ["FLT3-IDT", "−0.185±3.705", "36", "1.369±3.355", "17", "0.148"], ["IDH", "0.780±3.849", "39", "−0.986±2.683", "14", "0.120"], ["NPM1", "−0.022±3.925", "21", "0.533±3.485", "32", "0.592"], ["RUNX1", "0.295±3.740", "49", "0.535±2.373", "4", "0.901"], ["WT1", "0.354±3.762", "48", "−0.076±2.379", "5", "0.804"]], "row_count": 9, "column_count": 6, "numeric_cells": 36, "header_rows": 2, "locator": "section[7]/table-wrap[1]#T3"}}], 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Probes with P<0.05 were then selected for analysis in the GSE12417 dataset. Multivariate cox regression analysis (including age) was conducted to confirm whether the probes affect OS of CN-AML patients. 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