Identification and Validation of a Four-Long Non-coding RNA Signature Associated With Immune Infiltration and Prognosis in Colon Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34290738", "kind": "science-record", "revision": 7, "content_hash": "sha256:a344cfcb624b522bd24dcdb7fe405a7b08de9f7f549a35c5d364bce610d4d904", "created_at": "2026-11-01T15:41:44Z", "updated_at": "2026-11-01T22:04:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of a Four-Long Non-coding RNA Signature Associated With Immune Infiltration and Prognosis in Colon Cancer.", "doi": "10.3389/fgene.2021.671128", "pmid": "34290738", "authors": ["Yanbo Wang", "Jing Liu", "Fenghai Ren", "Yanjie Chu", "Binbin Cui"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "The emerging evidence has demonstrated the critical roles of long non-coding RNAs (lncRNAs) as regulators in the tumor immune microenvironment (TIME). However, the tumor immune infiltration-associated lncRNAs and their clinical significance in colon cancer have not yet been thoroughly investigated. This study performed an integrative analysis of lncRNA expression profiles and immune cell infiltration profiles and identified 258 immune infiltration-associated lncRNAs. Of them, four lncRNAs (AC008494.3, LINC00926, AC022034.1, and SNHG26) were significantly and independently associated with the patient's overall survival. Finally, we developed a tumor immune infiltration-associated lncRNA signature (TIILncSig) comprising of these four lncRNAs, which can divide colon cancer patients of The Cancer Genome Atlas (TCGA) into high-risk and low-risk groups with a significantly different outcome [Hazard ratio (HR) = 2.718, 95% CI = 1.955-3.779, p < 0.001]. Prognostic performance of the TIILncSig was further validated in another independent colon cancer cohort (HR = 1.832, 95% CI = 1.045-3.21, p = 0.034). Results of multivariate Cox regression and stratification analysis demonstrated that the TIILncSig is an independent predictive factor from other clinical features (HR = 2.687, 95% CI = 1.912-3.776, p < 0.001 for TCGA cohort and HR = 1.837, 95% CI = 1.047-3.223, p = 0.034 for GSE17538 cohort). Literature analysis provided experimental evidence supporting roles of the TIILncSig in cancer carcinogenesis and progression and immune regulation. Summary, our study will help to understand the mechanisms of lncRNAs in immune regulation in the tumor microenvironment and provide novel biomarkers or targets for prognosis prediction and therapy decision-making for patients with colon cancer.", "claims": [{"id": "claim-method", "statement": "The association between lncRNA expression and overall survival were evaluated using the univariate and multivariate Cox regression analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34290738", "locator": "sections[6] \"Statistical Analysis\" paragraph 2", "quote": "The association between lncRNA expression and overall survival were evaluated using the univariate and multivariate Cox regression analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found at: clinical and transcriptome data of colon cancer patients was downloaded from UCSC Xena Browser (http://xena.ucsc.edu/, GDC TCGA Colon Cancer cohort) and Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17536).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34290738", "locator": "sections[13] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found at: clinical and transcriptome data of colon cancer patients was downloaded from UCSC Xena Browser (http://xena.ucsc.edu/, GDC TCGA Colon Cancer cohort) and Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17536)."}], "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:34290738"], "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:GSE17536"], "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": ["data:geo:GSE17536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34290738", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.671128", "sha256": "sha256:64f11bc1f120b61c67508e2513b6039bd9929597417ae7057920c8e6d74ee61a", "bytes": 34715, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.671128", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8287327", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17536", "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=GSE17536", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17536", "version": null, "note": "Publicly available datasets were analyzed in this study. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:34290738", "data:geo:GSE17536", "asset:table:pmid:34290738:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE17536"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:39Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 27410, "completion_tokens": 2088, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:34290738", "type": "paper", "label": "pmid:34290738"}, {"id": "source:pmid:34290738", "type": "manuscript", "label": "PMID 34290738 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34290738", "type": "paper", "label": "pmid:34290738"}, {"id": "source:pmid:34290738", "type": "manuscript", "label": "PMID 34290738 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34290738", "type": "extraction", "used": ["source:pmid:34290738"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE17536", "type": "accession_resolution", "used": ["data:geo:GSE17536"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:34290738", "parent_hash": "sha256:118a98623002b1952406876d925ebc4a9641de1db51a2fe76c14dfda46298a8a", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE17536 licence not read", "asset:data:geo:GSE17536 not downloaded", "asset:data:geo:GSE17538 licence not read", "asset:data:geo:GSE17538 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Browser (GDC TCGA Colon Cancer cohort).1 The RNA-seq gene expression level 3 data [log2(RPKM +1)", ", a total of 3,959 lncRNAs were retained for RNA-seq data. For microarray data, a total of 5,919", "Materials and Methods Clinical and Transcriptomic Data of Colon Cancer Patients Clinical and t", "c Data of Colon Cancer Patients Clinical and transcriptomic data of 512 colon cancer patients were obtai"], "order_basis": "paper_text_order:1937", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rom Gene Expression Omnibus (GEO) database.2 Microarray data profiled by Affymetrix Human Genome U13", "lncRNAs were retained for RNA-seq data. For microarray data, a total of 5,919 lncRNAs were retained", "(GEO) database.2 Microarray data profiled by Affymetrix Human Genome U133 Plus 2.0 Array was used an"], "order_basis": "paper_text_order:2424", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The association between lncRNA expression and overall survival were evaluated using the univariate and multivariate Cox regression analysis."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}