Comprehensive analyses of A 12-metabolism-associated gene signature and its connection with tumor metastases in clear cell renal cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36949462", "kind": "science-record", "revision": 3, "content_hash": "sha256:db407338141b1079beaf09494b87c3c26879d61801819eefdf21ef1a08ce50a2", "created_at": "2026-11-01T19:01:35Z", "updated_at": "2026-11-01T22:09:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analyses of A 12-metabolism-associated gene signature and its connection with tumor metastases in clear cell renal cell carcinoma.", "doi": "10.1186/s12885-023-10740-6", "pmid": "36949462", "authors": ["Diaoyi Tan", "Daojia Miao", "Chuanyi Zhao", "Jian Shi", "Qingyang Lv", "Zhiyong Xiong", "Hongmei Yang", "Xiaoping Zhang"], "journal": "BMC cancer", "year": 2023, "abstract": "BACKGROUND: The outcomes of patients with clear cell renal cell carcinoma (ccRCC) were dreadful due to lethal local recurrence and distant metastases. Accumulating evidence suggested that ccRCC was considered a metabolic disease and metabolism-associated genes (MAGs) exerted essential functions in tumor metastases. Thus, this study intends to seek whether the dysregulated metabolism promotes ccRCC metastases and explores underlying mechanisms.\nMETHOD: Weighted gene co-expression network analysis (WGCNA) was employed based on 2131 MAGs to select genes mostly associated with ccRCC metastases for subsequent univariate Cox regression. On this basis, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were employed to create a prognostic signature based on the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) cohort. The prognostic signature was confirmed using E-MTAB-1980 and GSE22541 cohorts. Kaplan-Meier, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox regression were applied to detect the predictability and independence of the signature in ccRCC patients. Functional enrichment analyses, immune cell infiltration examinations, and somatic variant investigations were employed to detect the biological roles of the signature.\nRESULT: A 12-gene-metabolism-associated prognostic signature, termed the MAPS by our team, was constructed. According to the MAPS, patients were divided into low- and high-risk subgroups and high-risk patients displayed inferior outcomes. The MAPS was validated as an independent and reliable biomarker in ccRCC patients for forecasting the prognosis and progression of ccRCC patients. Functionally, the MAPS was closely associated with metabolism dysregulation, tumor metastases, and immune responses in which the high-risk tumors were in an immunosuppressive status. Besides, high-risk patients benefited more from immunotherapy and held a higher tumor mutation burden (TMB) than low-risk patients.\nCONCLUSION: The 12-gene MAPS with prominent biological roles could independently and reliably forecast the outcomes of ccRCC patients, and provide clues to uncover the latent mechanism in which dysregulated metabolism controlled ccRCC metastases.", "claims": [{"id": "claim-method", "statement": "Weighted gene co-expression network analysis (WGCNA) was employed based on 2131 MAGs to select genes mostly associated with ccRCC metastases for subsequent univariate Cox regression. On this basis, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were employed to create a prognostic signature based on the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36949462", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Weighted gene co-expression network analysis (WGCNA) was employed based on 2131 MAGs to select genes mostly associated with ccRCC metastases for subsequent univariate Cox regression. On this basis, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were employed to create a prognostic signature based on the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36949462", "locator": "sections[29] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 12-gene-metabolism-associated prognostic signature, termed the MAPS by our team, was constructed.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36949462", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A 12-gene-metabolism-associated prognostic signature, termed the MAPS by our team, was constructed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 12-gene-metabolism-associated prognostic signature, termed the MAPS by our team, was constructed.", "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:36949462"], "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:E-MTAB-1980"], "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:E-MTAB-1980"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36949462", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-023-10740-6", "sha256": "sha256:0e58129e01479a4bd42d33e9102cb0a1d7bb67278d6070f6fda5c96a3d506c24", "bytes": 78679, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-023-10740-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10035225", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-1980", "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=E-MTAB-1980", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-1980", "version": null, "note": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-10-31T18:28:57Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE105261", "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=GSE105261", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE105261", "version": null, "note": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2825239", "GSM2825240", "GSM2825241", "GSM2825242", "GSM2825243", "GSM2825244", "GSM2825245", "GSM2825246", "GSM2825247", "GSM2825248", "GSM2825249", "GSM2825250", "GSM2825251", "GSM2825252", "GSM2825253", "GSM2825254", "GSM2825255", "GSM2825256", "GSM2825257", "GSM2825258", "GSM2825259", "GSM2825260", "GSM2825261", "GSM2825262", "GSM2825263", "GSM2825264", "GSM2825265", "GSM2825266", "GSM2825267", "GSM2825268", "GSM2825269", "GSM2825270", "GSM2825271", "GSM2825272", "GSM2825273", "GSM2825274", "GSM2825275", "GSM2825276", "GSM2825277", "GSM2825278", "GSM2825279", "GSM2825280", "GSM2825281", "GSM2825282"], "sample_count": 44, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Transcriptome analysis of normal kidney, primary and metastasis ccRCC", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE22541", "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=GSE22541", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22541", "version": null, "note": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM359477", "GSM359478", "GSM359479", "GSM359480", "GSM359481", "GSM359482", "GSM359483", "GSM359484", "GSM359485", "GSM359486", "GSM359487", "GSM359488", "GSM359489", "GSM359490", "GSM359491", "GSM359492", "GSM359493", "GSM359494", "GSM359495", "GSM359496", "GSM559577", "GSM559578", "GSM559579", "GSM559580", "GSM559581", "GSM559582", "GSM559583", "GSM559584", "GSM559585", "GSM559586", "GSM559587", "GSM559588", "GSM559589", "GSM559590", "GSM559591", "GSM559592", "GSM559593", "GSM559594", "GSM559595", "GSM559596", "GSM559597", "GSM559598", "GSM559599", "GSM559600", "GSM559705", "GSM559706", "GSM559707", "GSM559708", "GSM559709", "GSM559710", "GSM559711", "GSM559712", "GSM559713", "GSM559714", "GSM559715", "GSM559716", "GSM559717", "GSM559718", "GSM559719", "GSM559720", "GSM559721", "GSM559722", "GSM559723", "GSM559724", "GSM559725", "GSM559726", "GSM559727", "GSM559728"], "sample_count": 68, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from pulmonary metastases and primary tumors of clear-cell renal cell carcinoma (ccRCC) with different disease-free survivals", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:E-MTAB-1980 not downloaded", "asset:data:geo:E-MTAB-1980 licence not read", "asset:data:geo:GSE105261 not downloaded", "asset:data:geo:GSE105261 licence not read", "asset:data:geo:GSE22541 not downloaded", "asset:data:geo:GSE22541 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Weighted gene co-expression network analysis (WGCNA) was employed based on 2131 MAGs to select genes mostly associated with ccRCC metastases for subsequent univariate Cox regression. On this basis, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were employed to create a prognostic signature based on the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) cohort."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-3", "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-4", "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-5", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson's correlation"}}, {"id": "method-6", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["GSE105261", "GSE22541", "E-MTAB-1980"], "resolved_accessions": ["GSE105261", "GSE22541", "E-MTAB-1980"], "statements": ["The datasets used in this article were derived from the TCGA database (https://portal.gdc.cancer.gov/), the GEO database (https://www.ncbi.nlm.nih.gov/geo/), the accession number involves GSE105261 and GSE22541) and the EMBL-EBI database (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/, the accession number involves E-MTAB-1980)."], "basis": "The paper names GSE105261, GSE22541, E-MTAB-1980 in GEO database 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:36949462", "data:geo:E-MTAB-1980"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-1980"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:34:12Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 20900, "completion_tokens": 1940, "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:36949462", "type": "paper", "label": "pmid:36949462"}, {"id": "source:pmid:36949462", "type": "manuscript", "label": "PMID 36949462 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36949462", "type": "paper", "label": "pmid:36949462"}, {"id": "source:pmid:36949462", "type": "manuscript", "label": "PMID 36949462 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36949462", "type": "extraction", "used": ["source:pmid:36949462"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-1980", "type": "accession_resolution", "used": ["data:geo:E-MTAB-1980"], "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:36949462", "parent_hash": "sha256:b159f332855d06fa0f9a2edde53e6fac2c4de35948fd085ebf3b43458fd01726", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:E-MTAB-1980 licence not read", "asset:data:geo:E-MTAB-1980 not downloaded", "asset:data:geo:GSE105261 licence not read", "asset:data:geo:GSE105261 not downloaded", "asset:data:geo:GSE22541 licence not read", "asset:data:geo:GSE22541 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": ["Weighted gene co-expression network analysis (WGCNA) was employed based on 2131 MAGs to select genes mostly associated with ccRCC metastases for subsequent univariate Cox regression. On this basis, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were employed to create a prognostic signature based on the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) cohort."], "order_basis": "analysis_only", "id": "assay:1"}]}