A Novel Set of Immune-associated Gene Signature predicts Biochemical Recurrence in Localized Prostate Cancer Patients after Radical Prostatectomy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33995646", "kind": "science-record", "revision": 6, "content_hash": "sha256:4ee9bf8a8591d6f356352a24ad37548ab59659c316a3219a3ab7e1a6a7ea686d", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T21:25:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Set of Immune-associated Gene Signature predicts Biochemical Recurrence in Localized Prostate Cancer Patients after Radical Prostatectomy.", "doi": "10.7150/jca.51059", "pmid": "33995646", "authors": ["Jiao-Chen Luan", "Qi-Jie Zhang", "Kai Zhao", "Xiang Zhou", "Liang-Yu Yao", "Tong-Tong Zhang", "Teng-Yue Zeng", "Jia-Dong Xia", "Ning-Hong Song"], "journal": "Journal of Cancer", "year": 2021, "abstract": "Background: Decision-making regarding biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) mainly relies on clinicopathological parameters with a low predictive accuracy. Currently, accumulating evidence suggests that immune-associated genes (IAGs) play irreplaceable roles in tumorigenesis, progression and metastasis. Considering the critical role of immune in PCa, we therefore attempted to identify the novel IAGs signature and validate its prognostic value that can better forecast the risk for BCR and guide clinical treatment. Methods: RNA-sequencing and corresponding clinicopathological data were downloaded from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was utilized to screen out the candidate module closely related to BCR, and univariate and LASSO Cox regression analyses were performed to build the gene signature. Kaplan-Meier (KM) survival analysis, time-dependent receiver operating curve (ROC), independent prognostic analysis and nomogram were also applied to evaluate the prognostic value of the signature. Besides, Gene ontology analysis (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to explore potential biological pathways. Results: A total of six IAGs (SSTR1, NFATC3, NRP1, TUBB3, IL1R1, GDF15) were eventually identified and used to establish a novel IAGs signature. The Kaplan-Meier analysis revealed that patients with low-risk scores had longer recurrence-free survival (RFS) than those with high-risk scores in both GSE70769 and TCGA cohorts. Further, our signature was also proven to be a valuable independent prognostic factor for BCR. We also constructed a nomogram based on the gene signature and related clinicopathologic features, which excellently predict 1-year, 3-year and 5-year prognosis of localized PCa patients after RP. Moreover, functional enrichment analysis demonstrated the vital biological processes, and stratified GSEA revealed that a crucial immune-related pathway (T cell receptor signaling pathway) was notably enriched in the high-risk group. Conclusions: We successfully developed a novel robust IAGs signature that is powerful in BCR prediction in localized PCa patients after RP, and created a prognostic nomogram. In addition, the signature might help clinicians in selecting high-risk subpopulation, predicting survival status of patients and promoting more individualized therapies than traditional clinical factors.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival curves displayed that localized PCa patients in the high-risk group had a significantly poorer recurrence-free survival (RFS) compared to those in the low-risk one (p < 0.0001) in the training database (Figure 2A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33995646", "locator": "sections[11] \"IAGs signature is an independent risk factor in localized PCa patients\" paragraph 2", "quote": "Kaplan-Meier survival curves displayed that localized PCa patients in the high-risk group had a significantly poorer recurrence-free survival (RFS) compared to those in the low-risk one (p < 0.0001) in the training database (Figure 2A)."}], "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:33995646"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33995646", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/jca.51059", "sha256": "sha256:c0e61b9ffd81e98d6eb2b77ffc9860c9e32271584b562c07c6fa1ae8b69644ae", "bytes": 32336, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/jca.51059", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8120173", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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 regression"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}, {"id": "method-4", "family": null, "specific": null, "label": "Kaplan–Meier survival analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Kaplan-Meier survival curves displayed that localized PCa patients in the high-risk group had a significantly poorer recurrence-free survival (RFS) compared to those in the low-risk one (p < 0.0001) in the training database (Figure 2A)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:33995646"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:34:35Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 22909, "completion_tokens": 2348, "cached_tokens": 792}}, "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:33995646", "type": "paper", "label": "pmid:33995646"}, {"id": "source:pmid:33995646", "type": "manuscript", "label": "PMID 33995646 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33995646", "type": "paper", "label": "pmid:33995646"}, {"id": "source:pmid:33995646", "type": "manuscript", "label": "PMID 33995646 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33995646", "type": "extraction", "used": ["source:pmid:33995646"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:33995646", "parent_hash": "sha256:588ccad1aa2cbaa4b2e52d789c8930c08b6cfba2b959f52476bcf1ac79a83cf2", "fork_of": null, "generation": 5}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "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": ["r BCR and guide clinical treatment. Methods: RNA-sequencing and corresponding clinicopathological data w", "m the Cancer Genome Atlas (TCGA) cohort. The RNA-seq data of GSE70769 were produced with Illumina", "th full-scale clinical information. Besides, RNA-sequencing (RNA-seq) expression profile of 379 patients", "inical information. Besides, RNA-sequencing (RNA-seq) expression profile of 379 patients was down"], "order_basis": "paper_text_order:698", "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": 0.93, "evidence": ["lied to validate. The whole RNA-seq data and microarray were log2 transformed and normalized with th"], "order_basis": "paper_text_order:3989", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}