Development of a copper metabolism-related gene signature in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36524120", "kind": "science-record", "revision": 3, "content_hash": "sha256:d00200f8bfb4394bd69f20f03f4a4b1566945da5618ff0166365768ea2565621", "created_at": "2026-11-01T19:01:02Z", "updated_at": "2026-11-01T22:08:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of a copper metabolism-related gene signature in lung adenocarcinoma.", "doi": "10.3389/fimmu.2022.1040668", "pmid": "36524120", "authors": ["Wuguang Chang", "Hongmu Li", "Leqi Zhong", "Tengfei Zhu", "Zenghao Chang", "Wei Ou", "Siyu Wang"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Purpose: The dysregulation of copper metabolism is closely related to the occurrence and progression of cancer. This study aims to investigate the prognostic value of copper metabolism-related genes (CMRGs) in lung adenocarcinoma (LUAD) and its characterization in the tumor microenvironment (TME).\nMethods: The differentially expressed CMRGs were identified in The Cancer Genome Atlas (TCGA) of LUAD. The least absolute shrinkage and selection operator regression (LASSO) and multivariate Cox regression analysis were used to establish the copper metabolism-related gene signature (CMRGs), which was also validated in Gene Expression Omnibus (GEO) database (GSE72094). The expression of key genes was verified by quantitative real-time PCR (qRT-PCR). Then, the CMRGS was used to develop a nomogram to predict the 1-year, 3-year, and 5-year overall survival (OS). In addition, differences in tumor mutation burden (TMB), biological characteristics and immune cell infiltration between high-risk and low-risk groups were systematically analyzed. Immunophenoscore (IPS) and an anti-PD-L1 immunotherapy cohort (IMvigor210) were used to verify whether CMRGS can predict the response to immunotherapy in LUAD.\nResults: 34 differentially expressed CMRGs were identified in the TCGA dataset, 11 of which were associated with OS. The CMRGS composed of 3 key genes (LOXL2, SLC31A2 and SOD3) had showed good clinical value and stratification ability in the prognostic assessment of LUAD patients. The results of qRT-PCR confirmed the expression of key CMRGs in LUAD and normal tissues. Then, all LUAD patients were divided into low-risk and high-risk groups based on median risk score. Those in the low-risk group had a significantly longer OS than those in the high-risk group (P<0.0001). The area under curve (AUC) values of the nomogram at 1, 3, and 5 years were 0.734, 0.735, and 0.720, respectively. Calibration curves comparing predicted and actual OS were close to ideal model, indicating a good consistency between prediction and actual observation. Functional enrichment analysis showed that the low-risk group was enriched in a large number of immune pathways. The results of immune infiltration analysis also confirmed that there were a variety of immune cell infiltration in the low-risk group. In addition, multiple immune checkpoints were highly expressed in the low-risk group and may benefit better from immunotherapy.\nConclusion: CMRGS is a promising biomarker to assess the prognosis of LUAD patients and may be serve as a guidance on immunotherapy.", "claims": [{"id": "claim-method", "statement": "The LASSO Cox regression algorithm was subsequently performed on OS-related CMRGs (p < 0.05) to further eliminate overfitting by “glmnet” package. Finally, CMRGS was constructed by multivariate stepwise Cox regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36524120", "locator": "sections[5] \"Construction and validation of CMRGS\" paragraph 2", "quote": "The LASSO Cox regression algorithm was subsequently performed on OS-related CMRGs (p < 0.05) to further eliminate overfitting by “glmnet” package. Finally, CMRGS was constructed by multivariate stepwise Cox regression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36524120", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The CMRGS stratified LUAD patients into groups with significantly different overall survival, with the low-risk group having longer OS.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "Those in the low-risk group had a significantly longer OS than those in the high-risk group (P<0.0001)."}, "evidence": [{"asset": "source:pmid:36524120", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Those in the low-risk group had a significantly longer OS than those in the high-risk group (P<0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The CMRGS stratified LUAD patients into groups with significantly different overall survival, with the low-risk group having longer OS.", "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:36524120"], "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:GSE72094"], "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:GSE72094"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36524120", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.1040668", "sha256": "sha256:3bd0452b1056628c8c6bb963d75dad368dbe2449ecdcfdd75ea07b9a0cfc049e", "bytes": 30603, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.1040668", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9744782", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE72094", "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=GSE72094", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE72094", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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