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pmid:36950684

Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer.

Songyun Zhao · Xin Zhang · Feng Gao · Hao Chi · Jinhao Zhang · Zhijia Xia · Chao Cheng · Jinhui Liu

Frontiers in endocrinology · 2023 doi:10.3389/fendo.2023.1145797

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Data

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title
Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer.
doi
10.3389/fendo.2023.1145797
pmid
36950684
authors array · 8 items
[0]
Songyun Zhao
[1]
Xin Zhang
[2]
Feng Gao
[3]
Hao Chi
[4]
Jinhao Zhang
[5]
Zhijia Xia
[6]
Chao Cheng
[7]
Jinhui Liu
journal
Frontiers in endocrinology
year
2023
abstract
Background: Ovarian cancer (OC) is one of the most common and most malignant gynecological malignancies in gynecology. On the other hand, dysregulation of copper metabolism (CM) is closely associated with tumourigenesis and progression. Here, we investigated the impact of genes associated with copper metabolism (CMRGs) on the prognosis of OC, discovered various CM clusters, and built a risk model to evaluate patient prognosis, immunological features, and therapy response. Methods: 15 CMRGs affecting the prognosis of OC patients were identified in The Cancer Genome Atlas (TCGA). Consensus Clustering was used to identify two CM clusters. lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters. The GSE63885 cohort was used as an external validation cohort. Expression of CM risk score-associated genes was verified by single-cell sequencing and quantitative real-time PCR (qRT-PCR). Nomograms were used to visually depict the clinical value of CMRGPS. Differences in clinical traits, immune cell infiltration, and tumor mutational load (TMB) between risk groups were also extensively examined. Tumour Immune Dysfunction and Rejection (TIDE) and Immune Phenotype Score (IPS) were used to validate whether CMRGPS could predict response to immunotherapy in OC patients. Results: In the TCGA and GSE63885 cohorts, we identified two CM clusters that differed significantly in terms of overall survival (OS) and tumor microenvironment. We then created a CMRGPS containing 11 genes to predict overall survival and confirmed its reliable predictive power for OC patients. The expression of CM risk score-related genes was validated by qRT-PCR. Patients with OC were divided into low-risk (LR) and high-risk (HR) groups based on the median CM risk score, with better survival in the LR group. The 5-year AUC value reached 0.74. Enrichment analysis showed that the LR group was associated with tumor immune-related pathways. The results of TIDE and IPS showed a better response to immunotherapy in the LR group. Conclusion: Our study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of patients with OC, offering new insights into individualized treatment.
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lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters.
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Publicly available datasets were analyzed in this study. This data can be found here: https://www.jianguoyun.com/p/DRXvaEYQ0pH7ChiK6vMEIAA.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36950684", "kind": "science-record", "revision": 2, "content_hash": "sha256:8522bde87906d73c263ab3b2bb8425c30a90e50f69eba294cd4b21c3db2d5b10", "created_at": "2026-11-01T19:01:36Z", "updated_at": "2026-11-01T21:30:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer.", "doi": "10.3389/fendo.2023.1145797", "pmid": "36950684", "authors": ["Songyun Zhao", "Xin Zhang", "Feng Gao", "Hao Chi", "Jinhao Zhang", "Zhijia Xia", "Chao Cheng", "Jinhui Liu"], "journal": "Frontiers in endocrinology", "year": 2023, "abstract": "Background: Ovarian cancer (OC) is one of the most common and most malignant gynecological malignancies in gynecology. On the other hand, dysregulation of copper metabolism (CM) is closely associated with tumourigenesis and progression. Here, we investigated the impact of genes associated with copper metabolism (CMRGs) on the prognosis of OC, discovered various CM clusters, and built a risk model to evaluate patient prognosis, immunological features, and therapy response.\nMethods: 15 CMRGs affecting the prognosis of OC patients were identified in The Cancer Genome Atlas (TCGA). Consensus Clustering was used to identify two CM clusters. lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters. The GSE63885 cohort was used as an external validation cohort. Expression of CM risk score-associated genes was verified by single-cell sequencing and quantitative real-time PCR (qRT-PCR). Nomograms were used to visually depict the clinical value of CMRGPS. Differences in clinical traits, immune cell infiltration, and tumor mutational load (TMB) between risk groups were also extensively examined. Tumour Immune Dysfunction and Rejection (TIDE) and Immune Phenotype Score (IPS) were used to validate whether CMRGPS could predict response to immunotherapy in OC patients.\nResults: In the TCGA and GSE63885 cohorts, we identified two CM clusters that differed significantly in terms of overall survival (OS) and tumor microenvironment. We then created a CMRGPS containing 11 genes to predict overall survival and confirmed its reliable predictive power for OC patients. The expression of CM risk score-related genes was validated by qRT-PCR. Patients with OC were divided into low-risk (LR) and high-risk (HR) groups based on the median CM risk score, with better survival in the LR group. The 5-year AUC value reached 0.74. Enrichment analysis showed that the LR group was associated with tumor immune-related pathways. The results of TIDE and IPS showed a better response to immunotherapy in the LR group.\nConclusion: Our study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of patients with OC, offering new insights into individualized treatment.", "claims": [{"id": "claim-method", "statement": "lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36950684", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.jianguoyun.com/p/DRXvaEYQ0pH7ChiK6vMEIAA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36950684", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.jianguoyun.com/p/DRXvaEYQ0pH7ChiK6vMEIAA."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 5-year AUC value reached 0.74.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36950684", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The 5-year AUC value reached 0.74."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 5-year AUC value reached 0.74.", "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:36950684"], "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:GSE63885"], "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:GSE63885"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36950684", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2023.1145797", "sha256": "sha256:1c107ca4ead1cff70f7e955e231ef6b90a1012ca10cd7e9e07be278b586a34a9", "bytes": 45064, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2023.1145797", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10025496", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE63885", "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=GSE63885", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE63885", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.jianguoyun.com/p/DRXvaEYQ0pH7ChiK6vMEIAA.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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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": "R1", "reachable": true, "accessions": ["GSE63885", "GSE9891"], "resolved_accessions": ["GSE63885", "GSE9891"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: https://www.jianguoyun.com/p/DRXvaEYQ0pH7ChiK6vMEIAA."], "basis": "The paper names GSE63885, GSE9891 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:36950684", "data:geo:GSE63885"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE63885"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:34:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11738, "completion_tokens": 1730, "cached_tokens": 264}}, "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:36950684", "type": "paper", "label": "pmid:36950684"}, {"id": "source:pmid:36950684", "type": "manuscript", "label": "PMID 36950684 full text"}, {"id": "data:geo:GSE63885", "type": "dataset", "label": "GEO GSE63885"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36950684", "type": "paper", "label": "pmid:36950684"}, {"id": "source:pmid:36950684", "type": "manuscript", "label": "PMID 36950684 full text"}, {"id": "data:geo:GSE63885", "type": "dataset", "label": "GEO GSE63885"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36950684", "type": "extraction", "used": ["source:pmid:36950684"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE63885", "type": "accession_resolution", "used": ["data:geo:GSE63885"], "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:36950684", "parent_hash": "sha256:6ce7ff0376609f3d2eb3e7da372758bc3d15b96701eabb5aec6e95b56521352a", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE63885 licence not read", "asset:data:geo:GSE63885 not downloaded", "asset:data:geo:GSE9891 licence not read", "asset:data:geo:GSE9891 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["d by single-cell sequencing and quantitative real-time PCR (qRT-PCR). Nomograms were used to visually d"], "order_basis": "paper_text_order:1044", "id": "assay:1"}, {"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": 0.8, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}