Comprehensive Analysis of APA Events and Their Association With Tumor Microenvironment in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33815479", "kind": "science-record", "revision": 7, "content_hash": "sha256:b5525f42f13cd68df75f13c5c3880c3a9972ea4607c5b49cc510828d09371e5a", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T22:03:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of APA Events and Their Association With Tumor Microenvironment in Lung Adenocarcinoma.", "doi": "10.3389/fgene.2021.645360", "pmid": "33815479", "authors": ["Yuchu Zhang", "Libing Shen", "Qili Shi", "Guofang Zhao", "Fajiu Wang"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "BACKGROUND: Alternative polyadenylation (APA) is a pervasive posttranscriptional mechanism regulating gene expression. However, the specific dysregulation of APA events and its potential biological or clinical significance in lung adenocarcinoma (LUAD) remain unclear.\nMETHODS: Here, we collected RNA-Seq data from two independent datasets: GSE40419 (n = 146) and The Cancer Genome Atlas (TCGA) LUAD (n = 542). The DaPars algorithm was employed to characterize the APA profiles in tumor and normal samples. Spearman correlation was used to assess the effects of APA regulators on 3' UTR changes in tumors. The Cox proportional hazard model was used to identify clinically relevant APA events and regulators. We stratified 512 patients with LUAD in the TCGA cohort through consensus clustering based on the expression of APA factors.\nFINDINGS: We identified remarkably consistent alternative 3' UTR isoforms between the two cohorts, most of which were shortened in LUAD. Our analyses further suggested that aberrant usage of proximal polyA sites resulted in escape from miRNA binding, thus increasing gene expression. Notably, we found that the 3' UTR lengths of the mRNA transcriptome were correlated with the expression levels of APA factors. We further identified that CPSF2 and CPEB3 may serve as key regulators in both datasets. Finally, four LUAD subtypes according to different APA factor expression patterns displayed distinct clinical results and oncogenic features related to tumor microenvironment including immune, metabolic, and hypoxic status.\nINTERPRETATION: Our analyses characterize the APA profiles among patients with LUAD and identify two key regulators for APA events in LUAD, CPSF2 and CPEB3, which could serve as the potential prognostic genes in LUAD.", "claims": [{"id": "claim-method", "statement": "To identify the differences in 3′ UTRs between tumor and normal samples, we utilized the paired Wilcoxon rank-sum test to determine the significance. RNA-Seq data and the corresponding clinical information from two independent LUAD cohorts including tumor and normal samples were downloaded from the TCGA data portal1 and NCBI Gene Expression Omnibus (GEO) under accession number GSE40419.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33815479", "locator": "sections[4] \"Characterization of APA Events\" paragraph 2", "quote": "To identify the differences in 3′ UTRs between tumor and normal samples, we utilized the paired Wilcoxon rank-sum test to determine the significance."}, {"asset": "source:pmid:33815479", "locator": "sections[3] \"Data Collection\" paragraph 2", "quote": "RNA-Seq data and the corresponding clinical information from two independent LUAD cohorts including tumor and normal samples were downloaded from the TCGA data portal1 and NCBI Gene Expression Omnibus (GEO) under accession number GSE40419."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33815479", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "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:33815479"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE40419"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE40419"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33815479", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.645360", "sha256": "sha256:20b877973f45136a8cd991487ba9b8015e02735e6fab75e47736478b8ee93811", "bytes": 40713, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.645360", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8012674", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE40419", "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=GSE40419", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE40419", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM993606", "GSM993607", "GSM993608", "GSM993610", "GSM993611", "GSM993612", "GSM993613", "GSM993614", "GSM993616", "GSM993617", "GSM993618", "GSM993619", "GSM993620", "GSM993621", "GSM993622", "GSM993623", "GSM993624", "GSM993625", "GSM993626", "GSM993627", "GSM993628", "GSM993629", "GSM993630", "GSM993631", "GSM993632", "GSM993633", "GSM993634", "GSM993635", "GSM993636", "GSM993637", "GSM993638", "GSM993639", "GSM993640", "GSM993641", "GSM993642", "GSM993643", "GSM993644", "GSM993645", "GSM993646", "GSM993647", "GSM993648", "GSM993649", "GSM993650", "GSM993651", "GSM993652", "GSM993653", "GSM993654", "GSM993655", "GSM993656", "GSM993657", "GSM993658", "GSM993659", "GSM993660", "GSM993661", "GSM993662", "GSM993663", "GSM993664", "GSM993665", "GSM993666", "GSM993667", "GSM993668", "GSM993669", "GSM993670", "GSM993671", "GSM993672", "GSM993673", "GSM993674", "GSM993675", "GSM993676", "GSM993677", "GSM993678", "GSM993679", "GSM993680", "GSM993681", "GSM993682", "GSM993683", "GSM993684", "GSM993685", "GSM993686", "GSM993687", "GSM993688", "GSM993689", "GSM993690", "GSM993691", "GSM993692", "GSM993693", "GSM993694", "GSM993695", "GSM993696", "GSM993697", "GSM993698", "GSM993699", "GSM993700", "GSM993701", "GSM993702", "GSM993703", "GSM993704", "GSM993705", "GSM993706", "GSM993707", "GSM993708", "GSM993709", "GSM993710", "GSM993711", "GSM993712", "GSM993713", "GSM993714", "GSM993715", "GSM993716", "GSM993717", "GSM993718", "GSM993719", "GSM993720", "GSM993721", "GSM993722", "GSM993723", "GSM993724", "GSM993725", "GSM993726", "GSM993727", "GSM993728", "GSM993729", "GSM993730", "GSM993731", "GSM993732", "GSM993733", "GSM993734", "GSM993735", "GSM993736", "GSM993737", "GSM993738", "GSM993739", "GSM993740", "GSM993741", "GSM993742", "GSM993743", "GSM993744", "GSM993745", "GSM993746", "GSM993747", "GSM993748", "GSM993749", "GSM993750", "GSM993751", "GSM993752", "GSM993753", "GSM993754", "GSM993755", "GSM993756", "GSM993757", "GSM993758", "GSM993759", "GSM993760", "GSM993761", "GSM993762", "GSM993763", "GSM993764", "GSM993765", "GSM993766", "GSM993767", "GSM993768", "GSM993769", "GSM993770", "GSM993771"], "sample_count": 164, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "The transcriptional landscape and mutational profile of lung adenocarcinoma", "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:GSE40419 not downloaded", "asset:data:geo:GSE40419 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "To identify the differences in 3′ UTRs between tumor and normal samples, we utilized the paired Wilcoxon rank-sum test to determine the significance. 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