EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34439264", "kind": "science-record", "revision": 7, "content_hash": "sha256:377f32edba6c8a0d79d26c697728fbf232ff50c91965d1ec42d230596270a514", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T22:47:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.", "doi": "10.3390/cancers13164110", "pmid": "34439264", "authors": ["Satoru Yonekura", "Kosuke Ueda"], "journal": "Cancers", "year": 2021, "abstract": "BACKGROUND: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma.\nMETHODS: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234).\nRESULTS: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes.\nCONCLUSION: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.", "claims": [{"id": "claim-method", "statement": "For the visualization of the overall survival (OS) and disease-specific survival (DSS), we used Kaplan–Meier plotting. The multivariate Cox regression analysis was performed to assess the prognostic impact of EVI2B gene expression as a continuous variable with the other parameters such as age at diagnosis, sex (male vs. female), disease stage at initial diagnosis, and tumor purity on tumor immune estimation resource (TIMER, https://cistrome.shinyapps.io/timer/, accessed on 6 December 2020, TIMER2.0, http://timer.comp-genomics.org/, accessed on 6 December 2020) [25,26]. Log-rank test was performed by the OSskcm [22]. Clinical data of patients with metastatic melanoma were obtained from cBioPortal (TCGA PanCancer Atlas, https://www.cbioportal.org/, accessed on 20 March 2020) [20,21]. OSskcm, an online tool for survival analysis with transcriptome information [22], was used to obtain the clinical data of GSE65904 [23] and GSE19234 [24], which both mostly consist of metastatic melanoma with gene expression data in tumor tissue.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34439264", "locator": "sections[3] \"2.1. Survival Analysis with EVI2B mRNA Level in the Public Database\" paragraph 2", "quote": "For the visualization of the overall survival (OS) and disease-specific survival (DSS), we used Kaplan–Meier plotting."}, {"asset": "source:pmid:34439264", "locator": "sections[3] \"2.1. Survival Analysis with EVI2B mRNA Level in the Public Database\" paragraph 2", "quote": "The multivariate Cox regression analysis was performed to assess the prognostic impact of EVI2B gene expression as a continuous variable with the other parameters such as age at diagnosis, sex (male vs. female), disease stage at initial diagnosis, and tumor purity on tumor immune estimation resource (TIMER, https://cistrome.shinyapps.io/timer/, accessed on 6 December 2020, TIMER2.0, http://timer.comp-genomics.org/, accessed on 6 December 2020) [25,26]."}, {"asset": "source:pmid:34439264", "locator": "sections[7] \"2.5. Statistical Analysis\" paragraph 2", "quote": "Log-rank test was performed by the OSskcm [22]."}, {"asset": "source:pmid:34439264", "locator": "sections[3] \"2.1. Survival Analysis with EVI2B mRNA Level in the Public Database\" paragraph 2", "quote": "Clinical data of patients with metastatic melanoma were obtained from cBioPortal (TCGA PanCancer Atlas, https://www.cbioportal.org/, accessed on 20 March 2020) [20,21]."}, {"asset": "source:pmid:34439264", "locator": "sections[3] \"2.1. Survival Analysis with EVI2B mRNA Level in the Public Database\" paragraph 2", "quote": "OSskcm, an online tool for survival analysis with transcriptome information [22], was used to obtain the clinical data of GSE65904 [23] and GSE19234 [24], which both mostly consist of metastatic melanoma with gene expression data in tumor tissue."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data used in this study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34439264", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "All the data used in this study are publicly available."}], "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:34439264"], "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 multivariate Cox regression analysis was performed to assess the prognostic impact of EVI2B gene expression as a continuous variable with the other parameters such as age at diagnosis, sex (male vs. female), disease stage at initial diagnosis, and tumor purity on tumor immune estimation resource (TIMER, https://cistrome.shinyapps.io/timer/, accessed on 6 December 2020, TIMER2.0, http://timer.comp-genomics.org/, accessed on 6 December 2020) [25,26]. Log-rank test was performed by the OSskcm [22]. Clinical data of patients with metastatic melanoma were obtained from cBioPortal (TCGA PanCancer Atlas, https://www.cbioportal.org/, accessed on 20 March 2020) [20,21]. OSskcm, an online tool for survival analysis with transcriptome information [22], was used to obtain the clinical data of GSE65904 [23] and GSE19234 [24], which both mostly consist of metastatic melanoma with gene expression data in tumor tissue."}}, {"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": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-4", "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": "hierarchical clustering"}}], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE65904", "GSE19234"], "resolved_accessions": ["GSE65904", "GSE19234"], "statements": ["All the data used in this study are publicly available."], "basis": "The paper names GSE65904, GSE19234 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:34439264", "data:geo:GSE19234", "asset:table:pmid:34439264:1", "asset:table:pmid:34439264:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE19234"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:05Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 29601, "completion_tokens": 2306, "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:34439264", "type": "paper", "label": "pmid:34439264"}, {"id": "source:pmid:34439264", "type": "manuscript", "label": "PMID 34439264 full text"}, {"id": "data:geo:GSE19234", "type": "dataset", "label": "GEO GSE19234"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34439264", "type": "paper", "label": "pmid:34439264"}, {"id": "source:pmid:34439264", "type": "manuscript", "label": "PMID 34439264 full text"}, {"id": "data:geo:GSE19234", "type": "dataset", "label": "GEO GSE19234"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34439264", "type": "extraction", "used": ["source:pmid:34439264"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE19234", "type": "accession_resolution", "used": ["data:geo:GSE19234"], "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:34439264", "parent_hash": "sha256:a7875578c926833c42530b1bde99cf6ea94214b717694a59f59c1f2bf6e5cf29", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE19234 licence not read", "asset:data:geo:GSE19234 not downloaded", "asset:data:geo:GSE65904 licence not read", "asset:data:geo:GSE65904 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["For the visualization of the overall survival (OS) and disease-specific survival (DSS), we used Kaplan–Meier plotting. The multivariate Cox regression analysis was performed to assess the prognostic impact of EVI2B gene expression as a continuous variable with the other parameters such as age at diagnosis, sex (male vs. female), disease stage at initial diagnosis, and tumor purity on tumor immune estimation resource (TIMER, https://cistrome.shinyapps.io/timer/, accessed on 6 December 2020, TIMER2.0, http://timer.comp-genomics.org/, accessed on 6 December 2020) [25,26]. Log-rank test was performed by the OSskcm [22]. Clinical data of patients with metastatic melanoma were obtained from cBioPortal (TCGA PanCancer Atlas, https://www.cbioportal.org/, accessed on 20 March 2020) [20,21]. OSskcm, an online tool for survival analysis with transcriptome information [22], was used to obtain the clinical data of GSE65904 [23] and GSE19234 [24], which both mostly consist of metastatic melanoma with gene expression data in tumor tissue."], "order_basis": "analysis_only", "id": "assay:1"}]}