Prognosis and personalized treatment prediction in lung adenocarcinoma: An in silico and in vitro strategy adopting cuproptosis related lncRNA towards precision oncology.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36874011", "kind": "science-record", "revision": 3, "content_hash": "sha256:96cc6eabbc6743485c37e807bf8896599c85fcf64743c1cc013c989ec38556d0", "created_at": "2026-11-01T19:01:30Z", "updated_at": "2026-11-01T22:08:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognosis and personalized treatment prediction in lung adenocarcinoma: An in silico and in vitro strategy adopting cuproptosis related lncRNA towards precision oncology.", "doi": "10.3389/fphar.2023.1113808", "pmid": "36874011", "authors": ["Chao Ma", "Feng Li", "Zhanfeng He", "Song Zhao", "Yang Yang", "Zhuoyu Gu"], "journal": "Frontiers in pharmacology", "year": 2023, "abstract": "Background: There is a rapid increase in lung adenocarcinomas (LUAD), and studies suggest associations between cuproptosis and the occurrence of various types of tumors. However, it remains unclear whether cuproptosis plays a role in LUAD prognosis. Methods: Dataset of the TCGA-LUAD was treated as training cohort, while validation cohort consisted of the merged datasets of the GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081. Ten studied cuproptosis-related genes (CRG) were used to generated CRG clusters and CRG cluster-related differential expressed gene (CRG-DEG) clusters. The differently expressed lncRNA that with prognosis ability between the CRG-DEG clusters were put into a LASSO regression for cuproptosis-related lncRNA signature (CRLncSig). Kaplan-Meier estimator, Cox model, receiver operating characteristic (ROC), time-dependent AUC (tAUC), principal component analysis (PCA), and nomogram predictor were further deployed to confirm the model's accuracy. We examined the model's connections with other forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The immunotherapy ability of the signature was demonstrated by applying eight mainstream immunoinformatic algorithms, TMB, TIDE, and immune checkpoints. We evaluated the potential drugs for high risk CRLncSig LUADs. Real-time PCR in human LUAD tissues were performed to verify the CRLncSig expression pattern, and the signature's pan-cancer's ability was also assessed. Results: A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort. Each of the signature genes was confirmed differentially expressed in the real world by real-time PCR. The CRLncSig correlated with 2,469/3,681 (67.07%) apoptosis-related genes, 13/20 (65.00%) necroptosis-related genes, 35/50 (70.00%) pyroptosis-related genes, and 238/380 (62.63%) ferroptosis-related genes. Immunotherapy analysis suggested that CRLncSig correlated with immune status, and checkpoints, KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, and CD28, were linked closely to our signature and were potentially suitable for LUAD immunotherapy targets. For those high-risk patients, we found three agents, gemcitabine, daunorubicin, and nobiletin. Finally, we found some of the CRLncSig lncRNAs potentially play a vital role in some types of cancer and need more attention in further studies. Conclusion: The results of this study suggest our cuproptosis-related CRLncSig can help to determine the outcome of LUAD and the effectiveness of immunotherapy, as well as help to better select targets and therapeutic agents.", "claims": [{"id": "claim-method", "statement": "In order to prevent overfitting, we performed the least absolute shrinkage and selection operator (LASSO) using the R package “glmnet” on the prognostic DELs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36874011", "locator": "sections[5] \"Constructions of CRG-DEG clusters and a cuproptosis-regulated lncRNA signature (CRLncSig)\" paragraph 2", "quote": "In order to prevent overfitting, we performed the least absolute shrinkage and selection operator (LASSO) using the R package “glmnet” on the prognostic DELs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: This study used publicly available datasets. Their names and where to get them are as follows: TCGA and pan-cancer TCGA TARGET GTEx, https://xenabrowser.net; GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081, https://www.ncbi.nlm.nih.gov/geo; CCLs database, https://depmap.org/portal; CTRP database, https://portals.broadinstitute.org/ctrp; PRISM database, https://depmap.org/portal/prism.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36874011", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: This study used publicly available datasets. Their names and where to get them are as follows: TCGA and pan-cancer TCGA TARGET GTEx, https://xenabrowser.net; GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081, https://www.ncbi.nlm.nih.gov/geo; CCLs database, https://depmap.org/portal; CTRP database, https://portals.broadinstitute.org/ctrp; PRISM database, https://depmap.org/portal/prism."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36874011", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A nine-lncRNA signature, CRLncSig, was built and demonstrated owning prognostic power by applied to the validation cohort.", "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:36874011"], "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:GSE29013"], "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:GSE29013"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36874011", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2023.1113808", "sha256": "sha256:2d53908c069182f28f54f6e446361685fc8c5313dda3bad0a618f8e9aa101eae", "bytes": 99239, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2023.1113808", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9975170", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE29013", "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=GSE29013", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE29013", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Their names and where to get them are as follows: TCGA and pan-cancer TCGA TARGET GTEx, https://xenabrowser.net; GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081, https://www.ncbi.nlm.nih.gov/geo; CCLs database, https://depmap.org/portal; CTRP database, https://portals.broadinstitute.org/ctrp; PRISM database, https://depmap.org/portal/prism.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM773540", "GSM773541", "GSM773542", "GSM773543", "GSM773544", "GSM773545", "GSM773546", "GSM773547", "GSM773548", "GSM773549", "GSM773550", "GSM773551", "GSM773552", "GSM773553", "GSM773554", "GSM773555", "GSM773556", "GSM773557", "GSM773558", "GSM773559", "GSM773560", "GSM773561", "GSM773562", "GSM773563", "GSM773564", "GSM773565", "GSM773566", "GSM773567", "GSM773568", "GSM773569", "GSM773570", "GSM773571", "GSM773572", "GSM773573", "GSM773574", "GSM773575", "GSM773576", "GSM773577", "GSM773578", "GSM773579", "GSM773580", "GSM773581", "GSM773582", "GSM773583", "GSM773584", "GSM773585", "GSM773586", "GSM773587", "GSM773588", "GSM773589", "GSM773590", "GSM773591", "GSM773592", "GSM773593", "GSM773594", "GSM773595", "GSM773596", "GSM773597", "GSM773598", "GSM773599", "GSM773600", "GSM773601", "GSM773602", "GSM773603", "GSM773604", "GSM773605", "GSM773606", "GSM773607", "GSM773608", "GSM773609", "GSM773610", "GSM773611", "GSM773612", "GSM773613", "GSM773614", "GSM773615", "GSM773616", "GSM773617", "GSM773618", "GSM773619", "GSM773620", "GSM773621", "GSM773622", "GSM773623", "GSM773624", "GSM773625", "GSM773626", "GSM773627", "GSM773628", "GSM773629", "GSM773630", "GSM773631", "GSM773632", "GSM773633", "GSM773634", "GSM773635", "GSM773636", "GSM773637", "GSM773638", "GSM773639", "GSM773640", "GSM773641", "GSM773642", "GSM773643", "GSM773644", "GSM773645", "GSM773646", "GSM773647", "GSM773648", "GSM773649", "GSM773650", "GSM773651", "GSM773652", "GSM773653", "GSM773654", "GSM773655", "GSM773656", "GSM773657", "GSM773658", "GSM773659", "GSM773660", "GSM773661", "GSM773662", "GSM773663", "GSM773664", "GSM773665", "GSM773666", "GSM773667", "GSM773668", "GSM773669", "GSM773670", "GSM773671", "GSM773672", "GSM773673", "GSM773674", "GSM773675", "GSM773676", "GSM773677", "GSM773678", "GSM773679", "GSM773680", "GSM773681", "GSM773682", "GSM773683", "GSM773684", "GSM773685", "GSM773686", "GSM773687", "GSM773688", "GSM773689", "GSM773690", "GSM773691", "GSM773692", "GSM773693", "GSM773694", "GSM773695", "GSM773696", "GSM773697", "GSM773698", "GSM773699", "GSM773700", "GSM773701", "GSM773702", "GSM773703", "GSM773704", "GSM773705", "GSM773706", "GSM773707", "GSM773708", "GSM773709", "GSM773710", "GSM773711", "GSM773712", "GSM773713", "GSM773714", "GSM773715", "GSM773716", "GSM773717", "GSM773718", "GSM773719", "GSM773720", "GSM773721", "GSM773722", "GSM773723", "GSM773724", "GSM773725", "GSM773726", "GSM773727", "GSM773728", "GSM773729", "GSM773730", "GSM773731", "GSM773732", "GSM773733", "GSM773734", "GSM773735", "GSM773736", "GSM773737", "GSM773738", "GSM773739", "GSM773740", "GSM773741", "GSM773742", "GSM773743", "GSM773744", "GSM773745", "GSM773746", "GSM773747", "GSM773748", "GSM773749", "GSM773750", "GSM773751", "GSM773752", "GSM773753", "GSM773754", "GSM773755", "GSM773756", "GSM773757", "GSM773758", "GSM773759", "GSM773760", "GSM773761", "GSM773762", "GSM773763", "GSM773764", "GSM773765", "GSM773766", "GSM773767", "GSM773768", "GSM773769", "GSM773770", "GSM773771", "GSM773772", "GSM773773", "GSM773774", "GSM773775", "GSM773776", "GSM773777", "GSM773778", "GSM773779", "GSM773780", "GSM773781", "GSM773782", "GSM773783", "GSM773784", "GSM773785"], "sample_count": 246, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression data for pathological stage I-II lung adenocarcinomas", "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:GSE37745", "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=GSE37745", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE37745", "version": null, "note": "Publicly available datasets were analyzed in this study. 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This data can be found here: This study used publicly available datasets. Their names and where to get them are as follows: TCGA and pan-cancer TCGA TARGET GTEx, https://xenabrowser.net; GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081, https://www.ncbi.nlm.nih.gov/geo; CCLs database, https://depmap.org/portal; CTRP database, https://portals.broadinstitute.org/ctrp; PRISM database, https://depmap.org/portal/prism.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: This study used publicly available datasets. 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181, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Validation of a histology-independent prognostic gene signature for early stage, non-small cell lung cancer including stage IA patients", "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:GSE29013 not downloaded", "asset:data:geo:GSE29013 licence not read", "asset:data:geo:GSE30219 not downloaded", "asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE37745 licence not read", "asset:data:geo:GSE50081 not downloaded", "asset:data:geo:GSE50081 licence not read"]}, "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 model"}}, {"id": "method-3", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "principal component analysis"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-5", "family": null, "specific": null, "label": "least absolute shrinkage and selection operator (LASSO) regression", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In order to prevent overfitting, we performed the least absolute shrinkage and selection operator (LASSO) using the R package “glmnet” on the prognostic DELs."}}], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "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": "R1", "reachable": true, "accessions": ["GSE29013", "GSE30219", "GSE31210", "GSE37745", "GSE50081"], "resolved_accessions": ["GSE29013", "GSE30219", "GSE31210", "GSE37745", "GSE50081"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: This study used publicly available datasets. Their names and where to get them are as follows: TCGA and pan-cancer TCGA TARGET GTEx, https://xenabrowser.net; GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081, https://www.ncbi.nlm.nih.gov/geo; CCLs database, https://depmap.org/portal; CTRP database, https://portals.broadinstitute.org/ctrp; PRISM database, https://depmap.org/portal/prism."], "basis": "The paper names GSE29013, GSE30219, GSE31210, GSE37745, GSE50081 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:36874011", "data:geo:GSE29013"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE29013"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:32:38Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 27356, "completion_tokens": 2159, "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:36874011", "type": "paper", "label": "pmid:36874011"}, {"id": "source:pmid:36874011", "type": "manuscript", "label": "PMID 36874011 full text"}, {"id": "data:geo:GSE29013", "type": "dataset", "label": "GEO GSE29013"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36874011", "type": "paper", "label": "pmid:36874011"}, {"id": "source:pmid:36874011", "type": "manuscript", "label": "PMID 36874011 full text"}, {"id": "data:geo:GSE29013", "type": "dataset", "label": "GEO GSE29013"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36874011", "type": "extraction", "used": ["source:pmid:36874011"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE29013", "type": "accession_resolution", "used": ["data:geo:GSE29013"], "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:36874011", "parent_hash": "sha256:16ec391c174a42e68f849d5e25ee74181e77eb5906fcccde55dca0513301692a", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE29013 licence not read", "asset:data:geo:GSE29013 not downloaded", "asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE30219 not downloaded", "asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE31210 not downloaded", "asset:data:geo:GSE37745 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE50081 licence not read", "asset:data:geo:GSE50081 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": 0.93, "evidence": ["her forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. T", "RLncSig correlated with 2,469/3,681 (67.07%) apoptosis-related genes, 13/20 (65.00%) necroptosis-re"], "order_basis": "paper_text_order:1193", "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": ["otential drugs for high risk CRLncSig LUADs. Real-time PCR in human LUAD tissues were performed to veri", "ifferentially expressed in the real world by real-time PCR. The CRLncSig correlated with 2,469/3,681 (6"], "order_basis": "paper_text_order:1462", "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"}]}