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pmid:34051812
The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML.
Chao Guo · Ya-Yue Gao · Qian-Qian Ju · Chun-Xia Zhang · Ming Gong · Zhen-Ling Li
Journal of translational medicine · 2021 doi:10.1186/s12967-021-02914-2
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Complete file
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We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA.\nMETHODS: We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and 'WGCNA' package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by 'glmnet' package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model.\nRESULTS: A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the 'lightyellow' module for NPM1 mutation, the 'saddlebrown' module for RUNX1 mutation, the 'lightgreen' module for TP53 mutation). ORA revealed that the 'lightyellow' module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The 'saddlebrown' module was enriched in immune response process. And the 'lightgreen' module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743-0.79).\nCONCLUSIONS: We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. 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"Homo sapiens", "title": "Prognostic gene signature for AML", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34051812:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:042f2e4879b79f798b16e3d98ab24ef0ce154fb9175c104a6d6da453ca8f2a52", "bytes": 1249, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#Tab1", "version": null, "note": "The clinical and genetic features of TCGA and BeatAML cohorts", "structure": {"pmcid": "PMC8164775", "section_index": 8, "section_title": "Results of WGCNA", "row_count": 30, "column_count": 3}, "table": {"label": "Table 1", "caption": "The clinical and genetic features of TCGA and BeatAML cohorts", "rows": [["", "BeatAML", "TCGA"], ["Patient number", "421", "136"], ["Female/male", "180/241", "61/75"], ["Median age (yr)", "61", "58"], ["Relapsed disease", "23(5.46%)", "NA"], ["MDS history", "41(9.74%)", "NA"], ["ELN2017 risk stratification"], ["Favorable", "101(24.0%)", "17(12.5%)"], ["Intermediate", "156(37.1%)", "80(58.8%)"], ["Poor", "163(38.7%)", "36(26.5%)"], ["Unknown", "1(0.2%)", "3(2.7%)"], ["ELN2017 prognostic markers"], ["Complex karyotype", "69(16.4%)", "18(13.2%)"], ["del(7)", "6(1.4%)", "NA"], ["RUNX1-RUNX1T1", "11(2.6%)", "6(4.4%)"], ["CBFB-MYH11", "10(2.4%)", "8(5.9%)"], ["CEBPA_Biallelic", "7(1.7%)", "13(9.6%)"], ["MLLT3-KMT2A", "13(3.1%)", "2(1.5%)"], ["DEK-NUP214", "3(0.7%)", "NA"], ["GATA2-MECOM", "8(1.9%)", "NA"], ["FLT3-ITD", "95(22.6%)", "38(27.9%)"], ["NPM1", "108(25.7%)", "38(27.9%)"], ["ASXL1", "31(7.4%)", "2(1.5%)"], ["RUNX1", "32(7.6%)", "14(10.3%)"], ["TP53", "27(6.4%)", "11(8.1%)"], ["5- or del(5q)", "NA", "3(2.2%)"], ["NPM1 (+) FLT3-ITD (−)", "59", "NA"], ["NPM1 (+) FLT3-ITD ( +)", "49", "NA"], ["NPM1 (−) FLT3-ITD (−)", "100", "NA"], ["NPM1 (−) FLT3-ITD ( +)", "46", "NA"]], "row_count": 30, "column_count": 3, "numeric_cells": 51, "header_rows": 1, "locator": "section[8]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34051812:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1bf596d9972bd6180aef8f58e2d4dbfd8cf7141ef720dd589c48a79643265442", "bytes": 820, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab2", "version": null, "note": "The prediction model for AML OS. The risk score of individual patients equals to the summation of products of included gene expression level and the corresponding coefficient", "structure": {"pmcid": "PMC8164775", "section_index": 12, "section_title": "Results of LASSO penalized regression analysis", "row_count": 7, "column_count": 4}, "table": {"label": "Table 2", "caption": "The prediction model for AML OS. The risk score of individual patients equals to the summation of products of included gene expression level and the corresponding coefficient", "rows": [["ENSEMBL ID", "Gene symbol", "Gene name", "Coefficent"], ["ENSG00000077150", "NFKB2", "Nuclear factor kappa B subunit 2", "0.04296"], ["ENSG00000119638", "NEK9", "NIMA related kinase 9", "0.070743"], ["ENSG00000122592", "HOXA7", "Homeobox A7", "0.055637"], ["ENSG00000136950", "ARPC5L", "Actin related protein 2/3 complex subunit 5 like", "0.748162"], ["ENSG00000226777", "FAM30A", "Family with sequence similarity 30 member A", "0.294823"], ["ENSG00000262050", "LOC105371592", "Uncharacterized LOC105371592", "0.031033"]], "row_count": 7, "column_count": 4, "numeric_cells": 19, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34051812:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2dea44325ad3329ebd0e31f18ad9ae1d6fd8940c36849d41c1561224f642ab00", "bytes": 1075, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#Tab3", "version": null, "note": "The results of univariate and multivariate Cox analysis of traditional prognostic factors and risk scores generated by the prediction model", "structure": {"pmcid": "PMC8164775", "section_index": 14, "section_title": "The validation of 6-gene signature model", "row_count": 12, "column_count": 7}, "table": {"label": "Table 3", "caption": "The results of univariate and multivariate Cox analysis of traditional prognostic factors and risk scores generated by the prediction model", "rows": [["", "Univariate Cox analysis", "Multivariate Cox analysis"], ["Characteristics", "Hazard Ratio", "95% CI", "p value", "Hazard Ratio", "95% CI", "p value"], ["Age", "1.03", "1.02–1.05", "0", "1.01", "0.99–1.03", "0.298"], ["Blast_percentage", "1", "0.99–1.02", "0.443", "NA", "NA", "NA"], ["FAB", "1.06", "0.94–1.2", "0.351", "NA", "NA", "NA"], ["Induction", "3.51", "2.19–5.61", "0", "1.84", "0.98–3.46", "0.057"], ["Race", "0.86", "0.66–1.13", "0.287", "NA", "NA", "NA"], ["Risk_cytogenetic", "1.73", "1.23–2.41", "0.001", "0.64", "0.22–1.92", "0.43"], ["Risk_molecular", "1.83", "1.31–2.56", "0", "3.36", "1.2–9.44", "0.021"], ["Riskscore", "1.01", "1–1.02", "0.012", "1.01", "1–1.02", "0.023"], ["Sex", "1.05", "0.69–1.57", "0.831", "NA", "NA", "NA"], ["Transplantation", "0.41", "0.27–0.62", "0", "0.42", "0.25–0.72", "0.002"]], "row_count": 12, "column_count": 7, "numeric_cells": 50, "header_rows": 2, "locator": "section[14]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE12417 not downloaded", "asset:data:geo:GSE12417 licence not read", "asset:data:geo:GSE37642 not downloaded", "asset:data:geo:GSE37642 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "dendrogram"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}], "targets": [], "gaps": []}, "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": true, "required_operations": ["hierarchical_cluster"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: hierarchical."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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