Comprehensive Analysis to Identify Enhancer-Regulated Inflammation-Associated Genes in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34539188", "kind": "science-record", "revision": 8, "content_hash": "sha256:b45444845ddf0ccea1eae76827b4b22613cdf7fc108714d081f4779bb3129f71", "created_at": "2026-11-01T15:41:52Z", "updated_at": "2026-11-01T22:47:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis to Identify Enhancer-Regulated Inflammation-Associated Genes in Lung Adenocarcinoma.", "doi": "10.2147/CMAR.S317922", "pmid": "34539188", "authors": ["Xi Li", "Xinling Li", "Lina Ding"], "journal": "Cancer management and research", "year": 2021, "abstract": "OBJECTIVE: The purpose of this study was to identify prognostic inflammatory markers regulated by enhancers in lung adenocarcinoma (LUAD).\nMETHODS: Inflammatory indices of 490 LUAD patients in TCGA database were calculated using genomic variation analysis (GSVA). Patients were divided into high- and low-inflammatory index groups. Fraction of 22 infiltrating immune cells was estimated using the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Gene set enrichment analysis (GSEA) was used to analyze gene enrichment. Differentially expressed genes were screened based on TCGA database. The H3K27ac ChIP-seq of A549 cells in GEO database (GSE42374) was analyzed to identify super enhancers. Kaplan-Meier method and multivariate Cox proportional hazards models were used for survival analysis. CCK8 and RT-qPCR were used for cellular level verification.\nRESULTS: Inflammation was associated with better outcome in LUAD patients. Anti-cancer immune cell fractions were upregulated in high-inflammatory index group. Genes enriched in inflammation-related signaling pathways were positively correlated with high-inflammatory index group. A total of 146 upregulated genes regulated by enhancers were screened, of which five genes including GDF10, HPGDS, ABCA8, SLIT3 and ADAMTS8 had significant influence on prognosis. ChIP-seq analysis showed that TGFβ+TNFα treatment promoted the enhancer activation of the five genes. Cellular experiments revealed that there was no significant effect of TGFβ treatment on the five genes expression. TNFα treatment upregulated the five genes expression, while the BET-bromodomain inhibitor JQ1 restored the effect of TNFα. Overexpression of the five genes significantly inhibited the proliferation of A549 and H1299 cells.\nCONCLUSION: GDF10, HPGDS, ABCA8, SLIT3 and ADAMTS8 were identified as enhancer-regulated prognostic inflammation-related biomarkers, and the expression of these genes inhibited proliferation of LUAD cells.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes in high-inflammatory index group compared with low-inflammatory index group were screened by “Limma” package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34539188", "locator": "sections[7] \"Identification of Differentially Expressed Genes and Enhancer-Regulated Genes\" paragraph 2", "quote": "Differentially expressed genes in high-inflammatory index group compared with low-inflammatory index group were screened by “Limma” package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data were included in the article and detailed enquiries can be made by contacting the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34539188", "locator": "sections[24] \"Data Sharing Statement\" paragraph 2", "quote": "All data were included in the article and detailed enquiries can be made by contacting the corresponding author."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34539188"], "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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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8445607", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE42374", "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=GSE42374", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42374", "version": null, "note": "All data were included in the article and detailed enquiries can be made by contacting the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data were included in the article and detailed enquiries can be made by contacting the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1038439", "GSM1038440", "GSM1038441", "GSM1038442", "GSM1038443", "GSM1038444", "GSM1038445", "GSM1038446", "GSM1038447", "GSM1038448", "GSM1038449", "GSM1038450", "GSM1038451", "GSM1038452", "GSM1038453", "GSM1038454", "GSM1038455", "GSM1038456", "GSM1038457", "GSM1038458", "GSM1038459", "GSM1038460", "GSM1038461", "GSM1038462", "GSM1038463", "GSM1038464", "GSM1038465", "GSM1038466", "GSM1038467", "GSM1038468", "GSM1038469", "GSM1038470", "GSM1038471", "GSM1038472", "GSM1038473", "GSM1038474"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "10999", "taxon": "Homo sapiens", "title": "Histone modification analysis in TGFbeta/TNFalpha treated A549 spheroid cultures", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE42374 not downloaded", "asset:data:geo:GSE42374 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed genes in high-inflammatory index group compared with low-inflammatory index group were screened by “Limma” package in R."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox proportional hazards"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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