Predicting lung adenocarcinoma prognosis, immune escape, and pharmacomic profile from arginine and proline-related genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37709932", "kind": "science-record", "revision": 3, "content_hash": "sha256:7286d76c30121482c6df77688a6325d5a7e7641c34b273a9229e2832f0ef56b9", "created_at": "2026-11-01T19:02:32Z", "updated_at": "2026-11-01T22:10:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Predicting lung adenocarcinoma prognosis, immune escape, and pharmacomic profile from arginine and proline-related genes.", "doi": "10.1038/s41598-023-42541-z", "pmid": "37709932", "authors": ["Ziqiang Wang", "Jing Zhang", "Shuhua Shi", "Hongyu Ma", "Dongqin Wang", "Chao Zuo", "Qiang Zhang", "Chaoqun Lian"], "journal": "Scientific reports", "year": 2023, "abstract": "Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that ranks first in morbidity and mortality. Abnormal arginine metabolism is associated with inflammatory lung disease and may influence alterations in the tumor immune microenvironment. However, the potential role of arginine and proline metabolic patterns and immune molecular markers in LUAD is unclear. Gene expression, somatic mutations, and clinicopathological information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was performed to identify metabolic genes associated with overall survival (OS). Unsupervised clustering divided the sample into two subtypes with different metabolic and immunological profiles. Gene set enrichment analysis (GESA) and gene set variation analysis (GSVA) were used to analyze the underlying biological processes of the two subtypes. Drug sensitivity between subtypes was also predicted; then prognostic features were developed by multivariate Cox regression analysis. In addition, validation was obtained in the GSE68465, and GSE50081 dataset. Then, gene expression, and clinical characterization of hub genes CPS1 and SMS were performed; finally, in vitro validation experiments for knockdown of SMS were performed in LUAD cell lines. In this study, we first identified 12 arginine and proline-related genes (APRGs) significantly associated with OS and characterized the clinicopathological features and tumor microenvironmental landscape of two different subtypes. Then, we established an arginine and proline metabolism-related scoring system and identified two hub genes highly associated with prognosis, namely CPS1, and SMS. In addition, we performed CCK8, transwell, and other functional experiments on SMS to obtain consistent results. Our comprehensive analysis revealed the potential molecular features and clinical applications of APRGs in LUAD. A model based on 2 APRGs can accurately predict survival outcomes in LUAD, improve our understanding of APRGs in LUAD, and pave a new pathway to guide risk stratification and treatment strategy development for LUAD patients.", "claims": [{"id": "claim-method", "statement": "To further explore the association between prognosis-related core genes and lung adenocarcinoma prognosis, we performed multivariate Cox regression analysis on 12 modeled genes and constructed a risk model based on genes related to arginine and proline metabolism", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37709932", "locator": "sections[11] \"Construction and validation of a prognostic model for ARG-related genes\" paragraph 2", "quote": "To further explore the association between prognosis-related core genes and lung adenocarcinoma prognosis, we performed multivariate Cox regression analysis on 12 modeled genes and constructed a risk model based on genes related to arginine and proline metabolism"}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37709932", "locator": "sections[34] \"Data availability\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the characteristic curve for simultaneously predicting 1-year, 3-year, and 5-year OS rates was 0.68, 0.64, and 0.61, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37709932", "locator": "sections[26] \"Establishing Arg and Pro metabolism-related profiles\" paragraph 2", "quote": "The area under the characteristic curve for simultaneously predicting 1-year, 3-year, and 5-year OS rates was 0.68, 0.64, and 0.61, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the characteristic curve for simultaneously predicting 1-year, 3-year, and 5-year OS rates was 0.68, 0.64, and 0.61, respectively.", "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:37709932"], "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:GSE30219"], "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:GSE30219"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37709932", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-023-42541-z", "sha256": "sha256:3e88edd984565cbcc9bc2853d67c8ec3d9be3fc0648fa58587d11be52819709a", "bytes": 67425, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-023-42541-z", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10502151", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30219", "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=GSE30219", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30219", "version": null, "note": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1465989", "GSM1465990", "GSM1465991", "GSM1465992", "GSM1465993", "GSM1465994", "GSM1465995", "GSM1465996", "GSM1465997", "GSM1465998", "GSM1465999", "GSM748053", "GSM748054", "GSM748055", "GSM748056", "GSM748057", "GSM748058", "GSM748059", "GSM748060", "GSM748061", "GSM748062", "GSM748063", "GSM748064", "GSM748065", "GSM748066", "GSM748067", "GSM748068", "GSM748069", "GSM748070", "GSM748071", "GSM748072", "GSM748073", "GSM748074", "GSM748075", "GSM748076", "GSM748077", "GSM748078", "GSM748079", "GSM748080", "GSM748081", "GSM748083", "GSM748084", "GSM748085", "GSM748086", "GSM748087", "GSM748088", "GSM748089", "GSM748090", "GSM748091", "GSM748092", "GSM748093", "GSM748094", "GSM748095", "GSM748096", "GSM748097", "GSM748098", "GSM748099", "GSM748100", "GSM748101", "GSM748102", "GSM748103", "GSM748104", "GSM748105", "GSM748106", "GSM748107", "GSM748108", "GSM748109", "GSM748110", "GSM748111", "GSM748112", "GSM748113", "GSM748115", "GSM748116", "GSM748117", "GSM748118", "GSM748119", "GSM748120", "GSM748121", "GSM748122", "GSM748123", "GSM748124", "GSM748125", "GSM748126", "GSM748127", "GSM748128", "GSM748129", "GSM748130", "GSM748131", "GSM748132", "GSM748133", "GSM748134", "GSM748135", "GSM748136", "GSM748137", "GSM748138", "GSM748139", "GSM748140", "GSM748141", "GSM748142", "GSM748143", "GSM748144", "GSM748145", "GSM748146", "GSM748147", "GSM748148", "GSM748149", "GSM748150", "GSM748151", "GSM748152", "GSM748153", "GSM748154", "GSM748155", "GSM748156", "GSM748157", "GSM748158", "GSM748159", "GSM748160", "GSM748161", "GSM748162", "GSM748163", "GSM748164", "GSM748165", "GSM748166", "GSM748167", "GSM748168", "GSM748169", "GSM748170", "GSM748171", "GSM748172", "GSM748173", "GSM748174", "GSM748175", "GSM748176", "GSM748177", "GSM748178", "GSM748179", "GSM748180", "GSM748181", "GSM748182", "GSM748183", "GSM748184", "GSM748185", "GSM748186", "GSM748187", "GSM748188", "GSM748189", "GSM748191", "GSM748192", "GSM748193", "GSM748195", "GSM748196", "GSM748197", "GSM748198", "GSM748199", "GSM748200", "GSM748201", "GSM748202", "GSM748203", "GSM748206", "GSM748207", "GSM748209", "GSM748210", "GSM748211", "GSM748212", "GSM748213", "GSM748214", "GSM748215", "GSM748216", "GSM748217", "GSM748218", "GSM748219", "GSM748220", "GSM748221", "GSM748222", "GSM748223", "GSM748224", "GSM748225", "GSM748226", "GSM748227", "GSM748228", "GSM748229", "GSM748232", "GSM748233", "GSM748234", "GSM748235", "GSM748239", "GSM748240", "GSM748242", "GSM748243", "GSM748244", "GSM748245", "GSM748246", "GSM748247", "GSM748248", "GSM748249", "GSM748250", "GSM748251", "GSM748252", "GSM748253", "GSM748254", "GSM748255", "GSM748256", "GSM748257", "GSM748258", "GSM748259", "GSM748260", "GSM748261", "GSM748262", "GSM748263", "GSM748264", "GSM748265", "GSM748266", "GSM748267", "GSM748268", "GSM748269", "GSM748270", "GSM748271", "GSM748272", "GSM748273", "GSM748274", "GSM748275", "GSM748276", "GSM748277", "GSM748278", "GSM748279", "GSM748280", "GSM748281", "GSM748282", "GSM748283", "GSM748284", "GSM748285", "GSM748286", "GSM748287", "GSM748288", "GSM748291", "GSM748292", "GSM748294", "GSM748295", "GSM748296", "GSM748297", "GSM748298", "GSM748299", "GSM748300", "GSM748301", "GSM748302", "GSM748303", "GSM748304", "GSM748305", "GSM748306", "GSM748307", "GSM748308", "GSM748309", "GSM748310", "GSM748311", "GSM748312", "GSM748313", "GSM748314", "GSM748315", "GSM748316", "GSM748317", "GSM748318", "GSM748319", "GSM748320", "GSM748321", "GSM748323", "GSM748324", "GSM748325", "GSM748326", "GSM748327", "GSM748328", "GSM748329", "GSM748330", "GSM748331", "GSM748332", "GSM748333", "GSM748334", "GSM748335", "GSM748336", "GSM748337", "GSM748338", "GSM748339", "GSM748341", "GSM748342", "GSM748343", "GSM748344", "GSM748345", "GSM748346", "GSM748347", "GSM748348", "GSM748349", "GSM748350", "GSM748351", "GSM748352", "GSM748353", "GSM748354", "GSM748355", "GSM748356", "GSM748357", "GSM748358", "GSM748359", "GSM748360", "GSM748361", "GSM748362", "GSM748363", "GSM748364", "GSM748365", "GSM748366"], "sample_count": 307, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "\"Off-context\" gene expression in lung cancer identifies a group of metastatic-prone tumors", "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; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1019138", "GSM1019139", "GSM1019140", "GSM1019141", "GSM1019142", "GSM1019143", "GSM1019144", "GSM1019145", "GSM1019146", "GSM1019147", "GSM1019148", "GSM1019149", "GSM1019150", "GSM1019151", "GSM1019152", "GSM1019153", "GSM1019154", "GSM1019155", "GSM1019156", "GSM1019157", "GSM1019158", "GSM1019159", "GSM1019160", "GSM1019161", "GSM1019162", "GSM1019163", "GSM1019164", "GSM1019165", "GSM1019166", "GSM1019167", "GSM1019168", "GSM1019169", "GSM1019170", "GSM1019171", "GSM1019172", "GSM1019173", "GSM1019174", "GSM1019175", "GSM1019176", "GSM1019177", "GSM1019178", "GSM1019179", "GSM1019180", "GSM1019181", "GSM1019182", "GSM1019183", "GSM1019184", "GSM1019185", "GSM1019186", "GSM1019187", "GSM1019188", "GSM1019189", "GSM1019190", "GSM1019191", "GSM1019192", "GSM1019193", "GSM1019194", "GSM1019195", "GSM1019196", "GSM1019197", "GSM1019198", "GSM1019199", "GSM1019200", "GSM1019201", "GSM1019202", "GSM1019203", "GSM1019204", "GSM1019205", "GSM1019206", "GSM1019207", "GSM1019208", "GSM1019209", "GSM1019210", "GSM1019211", "GSM1019212", "GSM1019213", "GSM1019214", "GSM1019215", "GSM1019216", "GSM1019217", "GSM1019218", "GSM1019219", "GSM1019220", "GSM1019221", "GSM1019222", "GSM1019223", "GSM1019224", "GSM1019225", "GSM1019226", "GSM1019227", "GSM1019228", "GSM1019229", "GSM1019230", "GSM1019231", "GSM1019232", "GSM1019233", "GSM1019234", "GSM1019235", "GSM1019236", "GSM1019237", "GSM1019238", "GSM1019239", "GSM1019240", "GSM1019241", "GSM1019242", "GSM1019243", "GSM1019244", "GSM1019245", "GSM1019246", "GSM1019247", "GSM1019248", "GSM1019249", "GSM1019250", "GSM1019251", "GSM1019252", "GSM1019253", "GSM1019254", "GSM1019255", "GSM1019256", "GSM1019257", "GSM1019258", "GSM1019259", "GSM1019260", "GSM1019261", "GSM1019262", "GSM1019263", "GSM1019264", "GSM1019265", "GSM1019266", "GSM1019267", "GSM1019268", "GSM1019269", "GSM1019270", "GSM1019271", "GSM1019272", "GSM1019273", "GSM1019274", "GSM1019275", "GSM1019276", "GSM1019277", "GSM1019278", "GSM1019279", "GSM1019280", "GSM1019281", "GSM1019282", "GSM1019283", "GSM1019284", "GSM1019285", "GSM1019286", "GSM1019287", "GSM1019288", "GSM1019289", "GSM1019290", "GSM1019291", "GSM1019292", "GSM1019293", "GSM1019294", "GSM1019295", "GSM1019296", "GSM1019297", "GSM1019298", "GSM1019299", "GSM1019300", "GSM1019301", "GSM1019302", "GSM1019303", "GSM1019304", "GSM1019305", "GSM1019306", "GSM1019307", "GSM1019308", "GSM1019309", "GSM1019310", "GSM1019311", "GSM1019312", "GSM1019313", "GSM1019314", "GSM1019315", "GSM1019316", "GSM1019317", "GSM1019318", "GSM1019319", "GSM1019320", "GSM1019321", "GSM1019322", "GSM1019323", "GSM1019324", "GSM1019325", "GSM1019326", "GSM1019327", "GSM1019328", "GSM1019329", "GSM1019330", "GSM1019331", "GSM1019332", "GSM1019333"], "sample_count": 196, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation", "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:GSE50081", "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=GSE50081", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50081", "version": null, "note": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. A statement that all methods and public data are implemented by relevant guidelines and regulations.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study; these can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo), and The Cancer Genome Atlas (https://portal.GDC.cancer.gov). The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials. The original R code has been uploaded to the authors’ GitHub homepage (https://github.com/wanglaoji2345/APRGs), and the corresponding data in the article are available from the corresponding author. 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In", "was considered significant. Cell culture and transfection Human lung adenocarcinoma cell lines A549 an", "ma Genetics (Shanghai, China). For transient transfection, A549 and H1299 cells were transfected with", "ient transfection, A549 and H1299 cells were transfected with siRNA for 12 h using a transfection rea"], "order_basis": "paper_text_order:1321", "id": "assay:1"}, {"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": ["ely CPS1, and SMS. In addition, we performed CCK8, transwell, and other functional experiments"], "order_basis": "paper_text_order:1794", "id": "assay:2"}, {"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": ["lture experiments using A549 and H1299 cells cultured in DMEM medium and RPMI 1640 medium (Gibco, The", "fection Human lung adenocarcinoma cell lines A549 and H1299 were mainly purchased from the cel", "performed in vitro culture experiments using A549 and H1299 cells cultured in DMEM medium and", "hanghai, China). For transient transfection, A549 and H1299 cells were transfected with siRNA"], "order_basis": "paper_text_order:3508", "id": "assay:3"}, {"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": ["To further explore the association between prognosis-related core genes and lung adenocarcinoma prognosis, we performed multivariate Cox regression analysis on 12 modeled genes and constructed a risk model based on genes related to arginine and proline metabolism"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}