Immune- and Stemness-Related Genes Revealed by Comprehensive Analysis and Validation for Cancer Immunity and Prognosis and Its Nomogram in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35833114", "kind": "science-record", "revision": 4, "content_hash": "sha256:446c2ee83cf4cdd6b15adb6d33c52fcce5291f2de3b1c67f95e2556e7b856b5f", "created_at": "2026-11-01T18:14:53Z", "updated_at": "2026-11-01T22:07:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune- and Stemness-Related Genes Revealed by Comprehensive Analysis and Validation for Cancer Immunity and Prognosis and Its Nomogram in Lung Adenocarcinoma.", "doi": "10.3389/fimmu.2022.829057", "pmid": "35833114", "authors": ["Mengqing Chen", "Xue Wang", "Wenjun Wang", "Xuemei Gui", "Zhan Li"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Objective: Lung adenocarcinoma (LUAD) is a familiar lung cancer with a very poor prognosis. This study investigated the immune- and stemness-related genes to develop model related with cancer immunity and prognosis in LUAD.\nMethod: The Cancer Genome Atlas (TCGA) was utilized for obtaining original transcriptome data and clinical information. Differential expression, prognostic value, and correlation with clinic parameter of mRNA stemness index (mRNAsi) were conducted in LUAD. Significant mRNAsi-related module and hub genes were screened using weighted gene coexpression network analysis (WGCNA). Meanwhile, immune-related differential genes (IRGs) were screened in LUAD. Stem cell index and immune-related differential genes (SC-IRGs) were screened and further developed to construct prognosis-related model and nomogram. Comprehensive analysis of hub genes and subgroups, involving enrichment in the subgroup [gene set enrichment analysis (GSEA)], gene mutation, genetic correlation, gene expression, immune, tumor mutation burden (TMB), and drug sensitivity, used bioinformatics and reverse transcription polymerase chain reaction (RT-PCR) for verification.\nResults: Through difference analysis, mRNAsi of LUAD group was markedly higher than that of normal group. Clinical parameters (age, gender, and T staging) were ascertained to be highly relevant to mRNAsi. MEturquoise and MEblue were found to be the most significant modules (including positive and negative correlations) related to mRNAsi via WGCNA. The functions and pathways of the two mRNAsi-related modules were mainly enriched in tumorigenesis, development, and metastasis. Combining stem cell index-related differential genes and immune-related differential genes, 30 prognosis-related SC-IRGs were screened via Cox regression analysis. Then, 16 prognosis-related SC-IRGs were screened to construct a LASSO regression model at last. In addition, the model was successfully validated by using TCGA-LUAD and GSE68465, whereas c-index and the calibration curves were utilized to demonstrate the clinical value of our nomogram. Following the validation of the model, GSEA, immune cell correlation, TMB, clinical relevance, etc., have found significant difference in high- and low-risk groups, and 16-gene expression of the SC-IRG model also was tested by RT-PCR. ADRB2, ANGPTL4, BDNF, CBLC, CX3CR1, and IL3RA were found markedly different expression between the tumor and normal group.\nConclusion: The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival. Our study used mRNAsi combined with immunity that may lay a foundation for the future research studies in LUAD.", "claims": [{"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the TCGA, GEO under the accession number GSE68465, Oncomine, TIMER, UALCAN, Kaplan–Meier Plotter, and GEPIA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35833114", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed during the current study are available in the TCGA, GEO under the accession number GSE68465, Oncomine, TIMER, UALCAN, Kaplan–Meier Plotter, and GEPIA."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35833114", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival.", "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:35833114"], "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:GSE68465"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE68465"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35833114", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.829057", "sha256": "sha256:ce5380321b697b56b24226db3a6ca401bec1f59488f6db8edc934c13d0f41b52", "bytes": 61599, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.829057", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9271778", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE68465", "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=GSE68465", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68465", "version": null, "note": "The datasets analyzed during the current study are available in the TCGA, GEO under the accession number GSE68465, Oncomine, TIMER, UALCAN, Kaplan–Meier Plotter, and GEPIA.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the current study are available in the TCGA, GEO under the accession number GSE68465, Oncomine, TIMER, UALCAN, Kaplan–Meier Plotter, and GEPIA.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1672281", "GSM1672282", "GSM1672283", "GSM1672284", "GSM1672285", "GSM1672286", "GSM1672287", "GSM1672288", "GSM1672289", "GSM1672290", "GSM1672291", "GSM1672292", "GSM1672293", "GSM1672294", "GSM1672295", "GSM1672296", "GSM1672297", "GSM1672298", "GSM1672299", "GSM1672300", "GSM1672301", "GSM1672302", "GSM1672303", "GSM1672304", "GSM1672305", "GSM1672306", "GSM1672307", "GSM1672308", "GSM1672309", "GSM1672310", "GSM1672311", "GSM1672312", "GSM1672313", "GSM1672314", "GSM1672315", "GSM1672316", "GSM1672317", "GSM1672318", "GSM1672319", "GSM1672320", "GSM1672321", "GSM1672322", "GSM1672323", "GSM1672324", "GSM1672325", "GSM1672326", "GSM1672327", "GSM1672328", "GSM1672329", "GSM1672330", "GSM1672331", "GSM1672332", "GSM1672333", "GSM1672334", "GSM1672335", "GSM1672336", "GSM1672337", "GSM1672338", "GSM1672339", "GSM1672340", "GSM1672341", "GSM1672342", "GSM1672343", "GSM1672344", "GSM1672345", "GSM1672346", "GSM1672347", "GSM1672348", "GSM1672349", "GSM1672350", "GSM1672351", "GSM1672352", "GSM1672353", "GSM1672354", "GSM1672355", "GSM1672356", "GSM1672357", "GSM1672358", "GSM1672359", "GSM1672360", "GSM1672361", "GSM1672362", "GSM1672363", "GSM1672364", "GSM1672365", "GSM1672366", "GSM1672367", "GSM1672368", "GSM1672369", "GSM1672370", "GSM1672371", "GSM1672372", "GSM1672373", "GSM1672374", "GSM1672375", "GSM1672376", "GSM1672377", "GSM1672378", "GSM1672379", "GSM1672380", "GSM1672381", "GSM1672382", "GSM1672383", "GSM1672384", "GSM1672385", "GSM1672386", "GSM1672387", "GSM1672388", "GSM1672389", "GSM1672390", "GSM1672391", "GSM1672392", "GSM1672393", "GSM1672394", "GSM1672395", "GSM1672396", "GSM1672397", "GSM1672398", "GSM1672399", "GSM1672400", "GSM1672401", "GSM1672402", "GSM1672403", "GSM1672404", "GSM1672405", "GSM1672406", "GSM1672407", "GSM1672408", "GSM1672409", "GSM1672410", "GSM1672411", "GSM1672412", "GSM1672413", "GSM1672414", "GSM1672415", "GSM1672416", "GSM1672417", "GSM1672418", "GSM1672419", "GSM1672420", "GSM1672421", "GSM1672422", "GSM1672423", "GSM1672424", "GSM1672425", "GSM1672426", "GSM1672427", "GSM1672428", "GSM1672429", "GSM1672430", "GSM1672431", "GSM1672432", "GSM1672433", "GSM1672434", "GSM1672435", "GSM1672436", "GSM1672437", "GSM1672438", "GSM1672439", "GSM1672440", "GSM1672441", "GSM1672442", "GSM1672443", "GSM1672444", "GSM1672445", "GSM1672446", "GSM1672447", "GSM1672448", "GSM1672449", "GSM1672450", "GSM1672451", "GSM1672452", "GSM1672453", "GSM1672454", "GSM1672455", "GSM1672456", "GSM1672457", "GSM1672458", "GSM1672459", "GSM1672460", "GSM1672461", "GSM1672462", "GSM1672463", "GSM1672464", "GSM1672465", "GSM1672466", "GSM1672467", "GSM1672468", "GSM1672469", "GSM1672470", "GSM1672471", "GSM1672472", "GSM1672473", "GSM1672474", "GSM1672475", "GSM1672476", "GSM1672477", "GSM1672478", "GSM1672479", "GSM1672480", "GSM1672481", "GSM1672482", "GSM1672483", "GSM1672484", "GSM1672485", "GSM1672486", "GSM1672487", "GSM1672488", "GSM1672489", "GSM1672490", "GSM1672491", "GSM1672492", "GSM1672493", "GSM1672494", "GSM1672495", "GSM1672496", "GSM1672497", "GSM1672498", "GSM1672499", "GSM1672500", "GSM1672501", "GSM1672502", "GSM1672503", "GSM1672504", "GSM1672505", "GSM1672506", "GSM1672507", "GSM1672508", "GSM1672509", "GSM1672510", "GSM1672511", "GSM1672512", "GSM1672513", "GSM1672514", "GSM1672515", "GSM1672516", "GSM1672517", "GSM1672518", "GSM1672519", "GSM1672520", "GSM1672521", "GSM1672522", "GSM1672523", "GSM1672524", "GSM1672525", "GSM1672526", "GSM1672527", "GSM1672528", "GSM1672529", "GSM1672530", "GSM1672531", "GSM1672532", "GSM1672533", "GSM1672534", "GSM1672535", "GSM1672536", "GSM1672537", "GSM1672538", "GSM1672539", "GSM1672540", "GSM1672541", "GSM1672542", "GSM1672543", "GSM1672544", "GSM1672545", "GSM1672546", "GSM1672547", "GSM1672548", "GSM1672549", "GSM1672550", "GSM1672551", "GSM1672552", "GSM1672553", "GSM1672554", "GSM1672555", "GSM1672556", "GSM1672557", "GSM1672558", "GSM1672559", "GSM1672560", "GSM1672561", "GSM1672562", "GSM1672563", "GSM1672564", "GSM1672565", "GSM1672566", "GSM1672567", "GSM1672568", "GSM1672569", "GSM1672570", "GSM1672571", "GSM1672572", "GSM1672573", "GSM1672574", "GSM1672575", "GSM1672576", "GSM1672577", "GSM1672578", "GSM1672579", "GSM1672580", "GSM1672581", "GSM1672582", "GSM1672583", "GSM1672584", "GSM1672585", "GSM1672586", "GSM1672587", "GSM1672588", "GSM1672589", "GSM1672590", "GSM1672591", "GSM1672592", "GSM1672593", "GSM1672594", "GSM1672595", "GSM1672596", "GSM1672597", "GSM1672598", "GSM1672599", "GSM1672600", "GSM1672601", "GSM1672602", "GSM1672603", "GSM1672604", "GSM1672605", "GSM1672606", "GSM1672607", "GSM1672608", "GSM1672609", "GSM1672610", "GSM1672611", "GSM1672612", "GSM1672613", "GSM1672614", "GSM1672615", "GSM1672616", "GSM1672617", "GSM1672618", "GSM1672619", "GSM1672620", "GSM1672621", "GSM1672622", "GSM1672623", "GSM1672624", "GSM1672625", "GSM1672626", "GSM1672627", "GSM1672628", "GSM1672629", "GSM1672630", "GSM1672631", "GSM1672632", "GSM1672633", "GSM1672634", "GSM1672635", "GSM1672636", "GSM1672637", "GSM1672638", "GSM1672639", "GSM1672640", "GSM1672641", "GSM1672642", "GSM1672643", "GSM1672644", "GSM1672645", "GSM1672646", "GSM1672647", "GSM1672648", "GSM1672649", "GSM1672650", "GSM1672651", "GSM1672652", "GSM1672653", "GSM1672654", "GSM1672655", "GSM1672656", "GSM1672657", "GSM1672658", "GSM1672659", "GSM1672660", "GSM1672661", "GSM1672662", "GSM1672663", "GSM1672664", "GSM1672665", "GSM1672666", "GSM1672667", "GSM1672668", "GSM1672669", "GSM1672670", "GSM1672671", "GSM1672672", "GSM1672673", "GSM1672674", "GSM1672675", "GSM1672676", "GSM1672677", "GSM1672678", "GSM1672679", "GSM1672680", "GSM1672681", "GSM1672682", "GSM1672683", "GSM1672684", "GSM1672685", "GSM1672686", "GSM1672687", "GSM1672688", "GSM1672689", "GSM1672690", "GSM1672691", "GSM1672692", "GSM1672693", "GSM1672694", "GSM1672695", "GSM1672696", "GSM1672697", "GSM1672698", "GSM1672699", "GSM1672700", "GSM1672701", "GSM1672702", "GSM1672703", "GSM1672704", "GSM1672705", "GSM1672706", "GSM1672707", "GSM1672708", "GSM1672709", "GSM1672710", "GSM1672711", "GSM1672712", "GSM1672713", "GSM1672714", "GSM1672715", "GSM1672716", "GSM1672717", "GSM1672718", "GSM1672719", "GSM1672720", "GSM1672721", "GSM1672722", "GSM1672723", "GSM1672724", "GSM1672725", "GSM1672726", "GSM1672727", "GSM1672728", "GSM1672729", "GSM1672730", "GSM1672731", "GSM1672732", "GSM1672733", "GSM1672734", "GSM1672735", "GSM1672736", "GSM1672737", "GSM1672738", "GSM1672739", "GSM1672740", "GSM1672741", "GSM1672742"], "sample_count": 462, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "caArray_jacob-00182: Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE68465 not downloaded", "asset:data:geo:GSE68465 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student t-test"}}, {"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 regression"}}, {"id": "method-3", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "dendrogram"}}], "targets": [], "gaps": ["method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE68465"], "resolved_accessions": ["GSE68465"], "statements": ["The datasets analyzed during the current study are available in the TCGA, GEO under the accession number GSE68465, Oncomine, TIMER, UALCAN, Kaplan–Meier Plotter, and GEPIA."], "basis": "The paper names GSE68465 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35833114", "data:geo:GSE68465"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE68465"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:55:15Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17349, "completion_tokens": 2066, "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:35833114", "type": "paper", "label": "pmid:35833114"}, {"id": "source:pmid:35833114", "type": "manuscript", "label": "PMID 35833114 full text"}, {"id": "data:geo:GSE68465", "type": "dataset", "label": "GEO GSE68465"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35833114", "type": "paper", "label": "pmid:35833114"}, {"id": "source:pmid:35833114", "type": "manuscript", "label": "PMID 35833114 full text"}, {"id": "data:geo:GSE68465", "type": "dataset", "label": "GEO GSE68465"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35833114", "type": "extraction", "used": ["source:pmid:35833114"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE68465", "type": "accession_resolution", "used": ["data:geo:GSE68465"], "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:35833114", "parent_hash": "sha256:d3bd7b4fd655e446c591ef528355566765e335aef430262fc10fc5a4d94a9e55", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE68465 licence not read", "asset:data:geo:GSE68465 not downloaded", "execution.not_run", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["n Type Culture Collection (USA). Beas-2B was cultured with Dulbecco’s modified Eagle medium (DMEM) cont", "tain A549 and HCC827 cell lines. Further, we cultured cells at 37°C with an atmosphere of 5% CO2.", "l cells (Beas-2B) and human LUAD cell lines (A549 and HCC827) from American Type Culture Colle", "rael) with 10% fetal bovine serum to sustain A549 and HCC827 cell lines. Further, we cultured"], "order_basis": "paper_text_order:5778", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student t-test"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}