Exploring necrosis-associated mitochondrial gene signatures: revealing their role in prognosis and immunotherapy of renal clear cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39023752", "kind": "science-record", "revision": 4, "content_hash": "sha256:a51f374c47fd6fe45887652fbd094fe6221382ea10766fb1935df324e1cca4bb", "created_at": "2026-11-01T20:29:06Z", "updated_at": "2026-11-01T22:54:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring necrosis-associated mitochondrial gene signatures: revealing their role in prognosis and immunotherapy of renal clear cell carcinoma.", "doi": "10.1007/s10238-024-01426-9", "pmid": "39023752", "authors": ["Zhipeng Wang", "Fuchun Zheng", "Shiliang Wei", "Sheng Li", "Situ Xiong", "Lei Zhang", "Liangwei Wan", "Songhui Xu", "Jun Deng", "Xiaoqiang Liu"], "journal": "Clinical and experimental medicine", "year": 2024, "abstract": "Mitochondrial dysfunction and necrotic apoptosis, pivotal in therapeutic strategies for multiple diseases, lack comprehensive understanding in the context of renal clear cell carcinoma (ccRCC). This study explores their potential as valuable tools for ccRCC prediction, prevention, and personalized medical care. Transcriptomic and clinical datasets were acquired from the Cancer Genome Atlas (TCGA) repository. Mitochondrial and necrosis-associated gene sets were sourced from MitoCarta3.0 and the KEGG Pathway databases, respectively. Six necrosis-related mitochondrial genes (nc-MTGs) with prognostic significance were analyzed and screened, and a prognostic model was constructed. The accuracy of the model was verified using external data (E-MTAB-1980). TISCH was used to explore nc-MTGs at the cellular level. Finally, the expression level of BH3 interacting domain death agonist (BID) in ccRCC cell line was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the effect of BID down-regulation on tumor cell migration was verified by transwell assays and wound-healing experiments. We established and validated a prognostic model for clear cell renal cell carcinoma (ccRCC) utilizing six necrosis-related mitochondrial genes (nc-MTGs), affirming its efficacy in evaluating tumor progression. RT-PCR results showed that BID expression was up-regulated in ccRCC tissues compared with controls and exhibited oncogenic effects. In vitro cell function experiments showed that BID may be an important factor affecting the migration of ccRCC. Our study is the first to elucidate the biological functions and prognostic significance of mitochondrial molecules related to necroptosis, providing a new way to evaluate mitochondrial therapeutics in patients with ccRCC.", "claims": [{"id": "claim-method", "statement": "We conducted thorough univariate Cox regression and LASSO regression analyses on 542 cancer patients from the TCGA database to identify the most critical mitochondrial genes (MTGs) for prognosis. Kaplan–Meier (K-M) survival curves were constructed using the log-rank test to assess overall survival (OS) outcomes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39023752", "locator": "sections[5] \"Construction and validation of prognostic signatures based on MTGs\" paragraph 2", "quote": "We conducted thorough univariate Cox regression and LASSO regression analyses on 542 cancer patients from the TCGA database to identify the most critical mitochondrial genes (MTGs) for prognosis."}, {"asset": "source:pmid:39023752", "locator": "sections[5] \"Construction and validation of prognostic signatures based on MTGs\" paragraph 3", "quote": "Kaplan–Meier (K-M) survival curves were constructed using the log-rank test to assess overall survival (OS) outcomes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data are from open access databases. TCGA database, Array Express database, MitoCarta3.0 databases, KEGG Pathway databases, and TCIA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39023752", "locator": "sections[31] \"notes\" paragraph 1", "quote": "All data are from open access databases. TCGA database, Array Express database, MitoCarta3.0 databases, KEGG Pathway databases, and TCIA database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We established and validated a prognostic model for clear cell renal cell carcinoma (ccRCC) utilizing six necrosis-related mitochondrial genes (nc-MTGs), affirming its efficacy in evaluating tumor progression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39023752", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We established and validated a prognostic model for clear cell renal cell carcinoma (ccRCC) utilizing six necrosis-related mitochondrial genes (nc-MTGs), affirming its efficacy in evaluating tumor progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We established and validated a prognostic model for clear cell renal cell carcinoma (ccRCC) utilizing six necrosis-related mitochondrial genes (nc-MTGs), affirming its efficacy in evaluating tumor progression.", "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:39023752"], "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:39023752", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10238-024-01426-9", "sha256": "sha256:fe0afb473708a95ce1faaf2ca823b9ed5af7863760bd135007d2025e98ef0ad5", "bytes": 42072, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10238-024-01426-9", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11258092", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "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": "All data are from open access databases. TCGA database, Array Express database, MitoCarta3.0 databases, KEGG Pathway databases, and TCIA database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data are from open access databases. TCGA database, Array Express database, MitoCarta3.0 databases, KEGG Pathway databases, and TCIA database.", "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}}], "gaps": ["asset:data:geo:E-MTAB-1980 not downloaded", "asset:data:geo:E-MTAB-1980 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": "reordered", "quote": "We conducted thorough univariate Cox regression and LASSO regression analyses on 542 cancer patients from the TCGA database to identify the most critical mitochondrial genes (MTGs) for prognosis. Kaplan–Meier (K-M) survival curves were constructed using the log-rank test to assess overall survival (OS) outcomes."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {"p_value": "multiple groups, with a p-value of 0"}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t test"}}, {"id": "method-3", "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": {"p_value": "multiple groups, with a p-value of 0"}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"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"}}], "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": ["E-MTAB-1980", "KIRC_GSE145281_aPDL1", "KIRC_GSE139555", "KIRC_GSE121636"], "resolved_accessions": ["E-MTAB-1980"], "statements": ["All data are from open access databases. TCGA database, Array Express database, MitoCarta3.0 databases, KEGG Pathway databases, and TCIA database."], "basis": "The paper names E-MTAB-1980 in Array Express 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:39023752", "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": "2026-11-01T19:24:29Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11377, "completion_tokens": 2734, "cached_tokens": 128}}, "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:39023752", "type": "paper", "label": "pmid:39023752"}, {"id": "source:pmid:39023752", "type": "manuscript", "label": "PMID 39023752 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:39023752", "type": "paper", "label": "pmid:39023752"}, {"id": "source:pmid:39023752", "type": "manuscript", "label": "PMID 39023752 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39023752", "type": "extraction", "used": ["source:pmid:39023752"], "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:39023752", "parent_hash": "sha256:30c704e5ca4f4ca86637301df95ee3e9a7bc17a5f5486c38a0dcf48a655d821a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:E-MTAB-1980 licence not read", "asset:data:geo:E-MTAB-1980 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Mitochondrial dysfunction and necrotic apoptosis, pivotal in therapeutic strategies for multi", "prognostic model mainly regulates cancer and apoptosis-related pathways, such as necroptosis, apopt", "tosis-related pathways, such as necroptosis, apoptosis, mitophagy, tumor transcriptional dysregulat"], "order_basis": "paper_text_order:144", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ence quantitative polymerase chain reaction (RT-qPCR), and the effect of BID down-regulation on t", "e quantitative polymerase chain reaction (RT-qPCR), and the effect of BID down-regulation on t"], "order_basis": "paper_text_order:1089", "id": "assay:2"}, {"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": ["We conducted thorough univariate Cox regression and LASSO regression analyses on 542 cancer patients from the TCGA database to identify the most critical mitochondrial genes (MTGs) for prognosis. Kaplan–Meier (K-M) survival curves were constructed using the log-rank test to assess overall survival (OS) outcomes."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}