Characterization of somatic mutation-associated microenvironment signatures in acute myeloid leukemia patients based on TCGA analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33149230", "kind": "science-record", "revision": 7, "content_hash": "sha256:8486b923d998834314a0c7753c49315c09783f4dcf5ab71aa0eb8bc11f0e8b26", "created_at": "2026-11-01T15:41:14Z", "updated_at": "2026-11-01T22:02:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Characterization of somatic mutation-associated microenvironment signatures in acute myeloid leukemia patients based on TCGA analysis.", "doi": "10.1038/s41598-020-76048-8", "pmid": "33149230", "authors": ["Jun Wang", "Feng-Ting Dao", "Lu Yang", "Ya-Zhen Qin"], "journal": "Scientific reports", "year": 2020, "abstract": "Recurrent genetic mutations occur in acute myeloid leukemia (AML) and have been incorporated into risk stratification to predict the prognoses of AML patients. The bone marrow microenvironment plays a critical role in the development and progression of AML. However, the characteristics of the genetic mutation-associated microenvironment have not been comprehensively identified to date. In this study, we obtained the gene expression profiles of 173 AML patients from The Cancer Genome Atlas (TCGA) database and calculated their immune and stromal scores by applying the ESTIMATE algorithm. Immune scores were significantly associated with OS and cytogenetic risk. Next, we categorized the intermediate and poor cytogenetic risk patients into individual-mutation and wild-type groups according to RUNX1, ASXL1, TP53, FLT3-ITD, NPM1 and biallelic CEBPA mutation status. The relationships between the immune microenvironment and each genetic mutation were investigated by identifying differentially expressed genes (DEGs) and conducting functional enrichment analyses of them. Significant immune- and stromal-relevant DEGs associated with each mutation were identified, and most of the DEGs (from the FLT3-ITD, NPM1 and biallelic CEBPA mutation groups) were validated in the GSE14468 cohort downloaded from the Gene Expression Omnibus (GEO) database. In summary, we identified key immune- and stromal-relevant gene signatures associated with genetic mutations in AML, which may provide new biomarkers for risk stratification and personalized immunotherapy.", "claims": [{"id": "claim-method", "statement": "Survival functions were estimated using the Kaplan–Meier method and were compared using the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33149230", "locator": "sections[18] \"Statistical analysis\" paragraph 2", "quote": "Survival functions were estimated using the Kaplan–Meier method and were compared using the log-rank test."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:33149230"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33149230", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-020-76048-8", "sha256": "sha256:13de20603c024f04bb1702ef460aa74c8f583a31ee2b1a99a249002023d57dfc", "bytes": 42214, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-020-76048-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7643165", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33149230:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dc414781cf72da87ae3e15240e808157e752685be21e1d6f472ab34d2fa516e8", "bytes": 806, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#Tab1", "version": null, "note": "Characteristics of somatic mutation-associated immune/stromal cell-relevant DEGs.", "structure": {"pmcid": "PMC7643165", "section_index": 9, "section_title": "Characteristics and prognostic significance of mutation-associated immune/stromal cell-relevant DEGs", "row_count": 8, "column_count": 5}, "table": {"label": "Table 1", "caption": "Characteristics of somatic mutation-associated immune/stromal cell-relevant DEGs.", "rows": [["Gene", "Immune", "Stroma"], ["Score(P values)", "Number of DEGs*(Mu vs WT)", "Score(P values)", "Number of DEGs*(Mu vs WT)"], ["RUNX1", "Mu > WT(0.15)", "Up: 8down: 0", "Mu > WT(0.0008)", "Up: 17down: 2"], ["TP53", "Mu > WT(0.35)", "Up: 24down: 2", "Mu > WT(0.089)", "UP: 41down: 0"], ["ASXL1", "Mu ≈ WT(0.91)", "Up: 0down: 0", "Mu > WT(0.014)", "Up: 7down: 1"], ["FLT3-ITD", "Mu < WT(0.061)", "Up: 0down: 7", "Mu < WT(0.022)", "Up: 2down: 20"], ["NPM1", "Mu ≈ WT(0.48)", "Up: 2down: 11", "Mu < WT(0.11)", "Up: 5down: 27"], ["biCEBPA", "Mu ≈ WT(0.88)", "Up: 1down: 2", "Mu ≈ WT(0.94)", "Up: 1down: 1"]], "row_count": 8, "column_count": 5, "numeric_cells": 25, "header_rows": 2, "locator": "section[9]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:33149230:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:47c7056769c56b95bcd285f31e6ff070a575bad51eb31a215f12b63aae92473a", "bytes": 1151, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab2", "version": null, "note": "FLT3-ITD, NPM1 and biCEBPA mutations-associated immune and stromal cell-relevant DEGs.", "structure": {"pmcid": "PMC7643165", "section_index": 10, "section_title": "Validation in the GEO database and identification of hub genes", "row_count": 7, "column_count": 4}, "table": {"label": "Table 2", "caption": "FLT3-ITD, NPM1 and biCEBPA mutations-associated immune and stromal cell-relevant DEGs.", "rows": [["Mutation", "Status of DEGs", "Immune cell-relevant DEGs", "Stromal cell-relevant DEGs"], ["FLT3-ITD mutation", "Upregulation", "None", "ENPP2; PTGIS (n = 2)"], ["Downregulation", "CD3D; CD48; GBP1; IL10RA; IL18RAP; IL2RB; LCK (n = 7)", "AOC3; BGN; C1QB; CDH5; COL15A1; COL1A2; COL3A1*; COL6A3; CXCL12*; DCN; EMCN*; FRZB*; ISLR; ITIH5*; KDR*; MXRA5*; PDE2A; RARRES2; TRAT1*; VCAM1* (n = 20)"], ["NPM1 mutation", "Upregulation", "CSTA; SRGN (n = 2)", "ADAMTS5*; C3AR1; F13A1; TNN; RASGRP3 (n = 5)"], ["Downregulation", "CD3D; CD48; GBP1; GZMB; HLA-DPA1; HLA-DPB1; IRF8; HLA-DRA; IL18RAP; RGS1; ZAP70 (n = 11)", "BGN; CD200; CD248; CDH5; COL1A2; COL6A3; COL8A2; CXCL12; DCN; EDIL3; ENPEP; ERG; FBLN2; FRZB; HGF; IL18R1; ISLR; ITIH5; ITM2A; MXRA5; PAPPA; PRKG1; SIGLEC1; SPON1*; SULF1; TRAT1; VCAM1 (n = 27)"], ["biCEBPA mutation", "Upregulation", "IL2RG (n = 1)", "ITM2A (n = 1)"], ["Downregulation", "GBP2; IL4R (n = 2)", "F13A1 (n = 1)"]], "row_count": 7, "column_count": 4, "numeric_cells": 11, "header_rows": 1, "locator": "section[10]/table-wrap[1]#Tab2"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival 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-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "Pathway enrichment"}}, {"id": "method-4", "family": null, "specific": null, "label": "Kaplan–Meier method", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Survival functions were estimated using the Kaplan–Meier method and were compared using the log-rank test."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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