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pmid:33193689
TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019.
Lianxiang Luo · Yushi Zheng · Mingyue Li · Xinjie Lin · Xiaodi Li · Xiaoling Li · Liao Cui · Hui Luo
Frontiers in genetics · 2020 doi:10.3389/fgene.2020.575770
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Complete file
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However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. 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"caption": "Correlation analysis between PRAD and related gene markers of immune cells.", "rows": [["Cell type", "Gene markers", "PRAD"], ["None", "Purity", "Age"], ["Cor", "p value", "Cor", "p value", "Cor", "p value"], ["B Cell", "CD19", "−0.125077723", "**", "−0.161441404", "***", "−0.130674148", "**"], ["CD27", "−0.148507385", "***", "−0.197633538", "***", "−0.147497971", "**"], ["CD38", "0.277349561", "***", "0.264768159", "***", "0.285518628", "***"], ["CD40", "−0.031102373", "0.488490749", "−0.065324277", "0.182988272", "−0.014884155", "0.743096953"], ["CD80", "−0.025275706", "0.573623548", "−0.000775715", "0.987399525", "−0.028181983", "0.5349634"], ["CXCR3", "−0.058626234", "0.191438313", "−0.092155904", "0.060097398", "−0.050598292", "0.264982434"], ["CXCR4", "−0.039409599", "0.213990606", "−0.060386012", "0.081356974", "−0.039569694", "0.217267393"], ["CXCR5", "−0.111933944", "*", "−0.147159268", "**", "−0.11526283", "*"], ["CXCR6", "0.04599172", "0.305688784", "0.004643028", "0.92465759", "0.054955353", "0.226065083"], ["CD24", "−0.026473203", "0.555471904", "−0.015678495", "0.749457539", "−0.022785709", "0.615822823"], ["NOTCH2", "0.385737482", "***", "0.412167843", "***", "0.38647116", "***"], ["TLR4", "0.058113222", "0.195428891", "0.037421509", "0.44597527", "0.07310733", "0.107103676"], ["FCRL2", "−0.0689383", "0.124444368", "−0.09415165", "0.054715415", "−0.06900531", "0.128331543"], ["MS4A1", "−0.050275534", "0.262784776", "−0.09070561", "0.064239045", "−0.051592392", "0.255799248"], ["CD8+ T cells", "CD8A", "−0.014071002", "0.754020343", "−0.057182925", "0.243844749", "−0.003878102", "0.931948835"], ["CD8B", "−0.253819947", "***", "−0.294883269", "***", "−0.239926201", "***"], ["Neutrophils", "FCGR3B", "0.227748682", "***", "0.192310891", "***", "0.239183779", "***"], ["CEACAM3", "−0.084244806", "0.060296919", "−0.124806186", "*", "−0.074381723", "0.10110602"], ["SIGLEC5", "0.127578293", "**", "0.108113169", "*", "0.137689965", "**"], ["FPR1", "0.017907041", "0.69005842", "0.005304498", "0.913962729", "0.018479869", "0.684049454"], ["CSF3R", "0.013799921", "0.758610788", "−0.007289568", "0.881968209", "0.024218738", "0.593795613"], ["S100A12", "0.101840483", "*", "0.050768182", "0.301009622", "0.103858731", "*"], ["CCR7", "−0.055605383", "0.0794254", "−0.095131944", "**", "−0.056713265", "0.07687487"], ["CD59", "0.051576816", "0.103784756", "−0.000217208", "0.995002609", "0.069817898", "*"], ["ITGAM", "0.01456332", "0.646192653", "−0.012419306", "0.72024322", "0.025774571", "0.421686702"], ["Macrophages", "CD68", "0.054701388", "0.222928601", "0.049576772", "0.312372981", "0.061720187", "0.173819383"], ["CD84", "0.194831995", "***", "0.192929791", "***", "0.201153192", "***"], ["CD163", "0.114147133", "*", "0.094016855", "0.05508935", "0.119318014", "**"], ["MS4A4A", "0.074285586", "0.09773774", "0.062607569", "0.201903638", "0.076906158", "0.090010272"], ["Th1", "STAT4", "−0.110499198", "*", "−0.143634834", "**", "−0.102844157", "*"], ["TBX21", "−0.050166722", "0.263820499", "−0.079626913", "0.104434358", "−0.03776681", "0.405637131"], ["CD4", "0.010785723", "0.810256304", "−0.016327057", "0.739565125", "0.017620344", "0.698106353"], ["STAT1", "0.251855636", "***", "0.243150567", "***", "0.262609113", "***"], ["IFNG", "0.008749306", "0.845579407", "0.023176929", "0.636977475", "0.004087266", "0.928313694"], ["Th2", "GATA3", "−0.052853373", "0.238972752", "−0.076308607", "0.119712115", "−0.040236079", "0.375482123"], ["CCR4", "0.102475485", "*", "0.087114627", "0.075573072", "0.109502291", "*"], ["CCR8", "0.083460773", "**", "0.082478046", "*", "0.080220846", "*"], ["Treg", "FOXP3", "0.098345298", "*", "0.092100968", "0.060230149", "0.103534079", "*"], ["STAT5B", "0.162853597", "***", "0.132678142", "**", "0.174846349", "***"], ["TGFB1", "−0.121657052", "**", "−0.130643512", "**", "−0.112691622", "*"], ["Monocyte", "CCL2", "−0.156503402", "***", "−0.160935808", "***", "−0.154647011", "***"], ["IL10", "0.102323948", "*", "0.084489676", "0.084846693", "0.105747627", "*"], ["VSIG4", "0.055510551", "0.216151232", "0.037773259", "0.441550846", "0.069920753", "0.123303746"], ["CSF1R", "0.021901893", "0.489925764", "0.003644287", "0.916307499", "0.02888442", "0.36786306"], ["FCGR2A", "0.04146666", "0.355778871", "0.043120956", "0.379769962", "0.046113184", "0.309841578"], ["FCER2", "−0.063291987", "0.158456007", "−0.091735378", "0.061259972", "−0.06412007", "0.157707324"], ["C3AR1", "0.081165021", "0.070351302", "0.075515738", "0.123613844", "0.089745028", "*"], ["CD86", "−0.047062539", "0.294553275", "−0.068561541", "0.162260698", "−0.043984262", "0.332733556"], ["Dendritic cells", "ITGAX", "−0.017242456", "0.700997541", "−0.023215473", "0.636282915", "−0.011063195", "0.807532086"], ["CD1C", "−0.060784439", "0.175639379", "−0.098711438", "*", "−0.0481207", "0.289228125"], ["NRP1", "0.066998266", "0.135388895", "0.081357421", "0.097078769", "0.079412634", "0.079992779"], ["THBD", "−0.045113816", "0.315023163", "−0.058283278", "0.234878596", "−0.034418563", "0.448556258"], ["HLA-DPA1", "−0.029792635", "0.507121538", "−0.057940216", "0.237756443", "−0.01996682", "0.660269707"], ["CD209", "0.13810813", "**", "0.100561136", "*", "0.150573382", "***"], ["NK cells", "KIR3DL3", "0.039328973", "0.381141308", "0.03331388", "0.497495954", "0.029879363", "0.510645775"], ["T Cell exhaustion", "PDCD1", "−0.157463315", "***", "−0.208662551", "***", "−0.153710866", "***"], ["CTLA4", "−0.14509021", "**", "−0.162964237", "***", "−0.146369875", "**"], ["LAG3", "−0.17683449", "***", "−0.211773634", "***", "−0.173234006", "***"], ["GZMB", "−0.102999687", "*", "−0.120962856", "*", "−0.10075826", "*"]], "row_count": 62, "column_count": 8, "numeric_cells": 294, "header_rows": 3, "locator": "section[17]/table-wrap[3]#tab3"}}], "gaps": ["asset:data:geo:GSE30589 not downloaded", "asset:data:geo:GSE30589 licence not read", "asset:data:geo:GSE52920 not downloaded", "asset:data:geo:GSE52920 licence not read", "asset:data:geo:GSE56677 not downloaded", "asset:data:geo:GSE56677 licence not read", "asset:data:geo:GSE6956 not downloaded", "asset:data:geo:GSE6956 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"hazard_ratio": "P/log-rank p value and hazard ratio with 95% intervals", "p_value": "Cox P/log-rank p value and hazard ratio with 9"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We calculated the Cox P/log-rank p value and hazard ratio with 95% intervals."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "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": ["GSE30589", "GSE56677", "GSE52920", "GSE6956"], "resolved_accessions": ["GSE30589", "GSE56677", "GSE52920", "GSE6956"], "statements": ["All datasets presented in this study are included in the article/supplementary material."], "basis": "The paper names GSE30589, GSE56677, GSE52920, GSE6956 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": ["logrank_test"], "assets": ["source:pmid:33193689", "data:geo:GSE30589", "asset:table:pmid:33193689:1", "asset:table:pmid:33193689:2", "asset:table:pmid:33193689:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30589"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 26603, "completion_tokens": 3310, "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:33193689", "type": "paper", "label": "pmid:33193689"}, {"id": "source:pmid:33193689", "type": "manuscript", "label": "PMID 33193689 full text"}, {"id": "data:geo:GSE30589", "type": "dataset", "label": "GEO GSE30589"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33193689", "type": "paper", "label": "pmid:33193689"}, {"id": "source:pmid:33193689", "type": "manuscript", "label": "PMID 33193689 full text"}, {"id": "data:geo:GSE30589", "type": "dataset", "label": "GEO GSE30589"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33193689", "type": "extraction", "used": ["source:pmid:33193689"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30589", "type": "accession_resolution", "used": ["data:geo:GSE30589"], "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:33193689", "parent_hash": "sha256:1035b143ea1a20f265c4b4c9bc21fc470ed8fd296efa8876808803b7f38d73ec", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE30589 licence not read", "asset:data:geo:GSE30589 not downloaded", "asset:data:geo:GSE52920 licence not read", "asset:data:geo:GSE52920 not downloaded", "asset:data:geo:GSE56677 licence not read", "asset:data:geo:GSE56677 not downloaded", "asset:data:geo:GSE6956 licence not read", "asset:data:geo:GSE6956 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ENEMANIA database. 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