Development of a novel embryonic germline gene-related prognostic model of lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34721973", "kind": "science-record", "revision": 4, "content_hash": "sha256:deb18b0d05b4d03ddca2a0bcc8e6b0eebe9f7ccb9ddc5eaddfe0c10a3e85c7ee", "created_at": "2026-11-01T17:36:24Z", "updated_at": "2026-11-01T22:05:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of a novel embryonic germline gene-related prognostic model of lung adenocarcinoma.", "doi": "10.7717/peerj.12257", "pmid": "34721973", "authors": ["Linjun Liu", "Ke Xu", "Yubai Zhou"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Emerging evidence implicates the correlation of embryonic germline genes with the tumor progress and patient's outcome. However, the prognostic value of these genes in lung adenocarcinoma (LUAD) has not been fully studied. Here we systematically evaluated this issue, and constructed a novel signature and a nomogram associated with embryonic germline genes for predicting the outcomes of lung adenocarcinoma.\nMETHODS: The LUAD cohorts retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used as training set and testing set, respectively. The embryonic germline genes were downloaded from the website https://venn.lodder.dev. Then, the differentially expressed embryonic germline genes (DEGGs) between the tumor and normal samples were identified by limma package. The functional enrichment and pathway analyses were also performed by clusterProfiler package. The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. Survival and Receiver Operating Characteristic (ROC) analyses were performed to validate the model using training set and four testing GEO datasets. Finally, a prognostic nomogram based on the signature genes was constructed using multivariate regression method.\nRESULTS: Among the identified 269 DEGGs, 249 were up-regulated and 20 were down-regulated. GO and KEGG analyses revealed that these DEGGs were mainly enriched in the process of cell proliferation and DNA damage repair. Then, 103 DEGGs with prognostic value were identified by univariate Cox regression and further filtered by LASSO method. The resulting sixteen DEGGs were included in step multivariate Cox regression and an eleven embryonic germline gene related signature (EGRS) was constructed. The model could robustly stratify the LUAD patients into high-risk and low-risk groups in both training and testing sets, and low-risk patients had much better outcomes. The multi-ROC analysis also showed that the EGRS model had the best predictive efficacy compared with other common clinicopathological factors. The EGRS model also showed robust predictive ability in four independent external datasets, and the area under curve (AUC) was 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094). More importantly, the expression level of some genes in EGRS has a significant correlation with the progression of LUAD clinicopathology, suggesting these genes might play an important role in the progression of LUAD. Finally, based on EGRS genes, we built and calibrated a nomogram for conveniently evaluating patients' outcomes.", "claims": [{"id": "claim-method", "statement": "The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34721973", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe raw data are available at TCGA and GEO.\nTCGA: TCGA-LUAD, TCGA-LUSC, TCGA-BRCA, TCGA-GBM, TCGA-OV, TCGA-UCEC, TCGA-KIRC, TCGA-HNSC, TCGA-LGG, TCGA-THCA, TCGA-PRAD, TCGA-SKCM, TCGA-COAD, TCGA-STAD, TCGA-BLCA, TCGA-LIHC, TCGA-CESC, TCGA-KIRP, TCGA-SARC, TCGA-LAML, TCGA-PAAD, TCGA-ESCA, TCGA-PCPG, TCGA-READ, TCGA-TGCT, TCGA-THYM, TCGA-KICH, TCGA-ACC, TCGA-MESO, TCGA-UVM, TCGA-DLBC, TCGA-UCS and TCGA-CHOL.\nGEO: GSE30219, GSE50081, GSE37745 and GSE72094.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34721973", "locator": "sections[28] \"Data Availability Statement\" paragraphs 1-5", "quote": "The following information was supplied regarding data availability:\nThe raw data are available at TCGA and GEO.\nTCGA: TCGA-LUAD, TCGA-LUSC, TCGA-BRCA, TCGA-GBM, TCGA-OV, TCGA-UCEC, TCGA-KIRC, TCGA-HNSC, TCGA-LGG, TCGA-THCA, TCGA-PRAD, TCGA-SKCM, TCGA-COAD, TCGA-STAD, TCGA-BLCA, TCGA-LIHC, TCGA-CESC, TCGA-KIRP, TCGA-SARC, TCGA-LAML, TCGA-PAAD, TCGA-ESCA, TCGA-PCPG, TCGA-READ, TCGA-TGCT, TCGA-THYM, TCGA-KICH, TCGA-ACC, TCGA-MESO, TCGA-UVM, TCGA-DLBC, TCGA-UCS and TCGA-CHOL.\nGEO: GSE30219, GSE50081, GSE37745 and GSE72094."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The AUC in four independent GEO datasets were 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094) (Figs. 6G–6J).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34721973", "locator": "sections[13] \"The validation of the EGRS for survival prediction\" paragraph 5", "quote": "The AUC in four independent GEO datasets were 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094) (Figs. 6G–6J)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The AUC in four independent GEO datasets were 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094) (Figs. 6G–6J).", "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:34721973"], "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. 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"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": "The following information was supplied regarding data availability:\nThe raw data are available at TCGA and GEO.\nTCGA: TCGA-LUAD, TCGA-LUSC, TCGA-BRCA, TCGA-GBM, TCGA-OV, TCGA-UCEC, TCGA-KIRC, TCGA-HNSC, TCGA-LGG, TCGA-THCA, TCGA-PRAD, TCGA-SKCM, TCGA-COAD, TCGA-STAD, TCGA-BLCA, TCGA-LIHC, TCGA-CESC, TCGA-KIRP, 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adenocarcinoma", "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:GSE30219 not downloaded", "asset:data:geo:GSE30219 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", "asset:data:geo:GSE72094 not downloaded", "asset:data:geo:GSE72094 licence not read"]}, "analysis": {"state": "complete", "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": "The prognostic model was constructed by the least absolute shrinkage and selection 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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": ["GSE30219", "GSE50081", "GSE37745", "GSE72094"], "resolved_accessions": ["GSE30219", "GSE50081", "GSE37745", "GSE72094"], "statements": ["The following information was supplied regarding data availability:\nThe raw data are available at TCGA and GEO.\nTCGA: TCGA-LUAD, TCGA-LUSC, TCGA-BRCA, TCGA-GBM, TCGA-OV, TCGA-UCEC, TCGA-KIRC, TCGA-HNSC, TCGA-LGG, TCGA-THCA, TCGA-PRAD, TCGA-SKCM, TCGA-COAD, TCGA-STAD, TCGA-BLCA, TCGA-LIHC, TCGA-CESC, TCGA-KIRP, TCGA-SARC, TCGA-LAML, TCGA-PAAD, TCGA-ESCA, TCGA-PCPG, TCGA-READ, TCGA-TGCT, TCGA-THYM, TCGA-KICH, TCGA-ACC, TCGA-MESO, TCGA-UVM, TCGA-DLBC, TCGA-UCS and TCGA-CHOL.\nGEO: GSE30219, GSE50081, GSE37745 and GSE72094."], "basis": "The paper names GSE30219, GSE50081, GSE37745, GSE72094 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": ["cox_ph"], "assets": ["source:pmid:34721973", "data:geo:GSE30219"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30219"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:05:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17646, "completion_tokens": 2748, "cached_tokens": 0}}, "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:34721973", "type": "paper", "label": "pmid:34721973"}, {"id": "source:pmid:34721973", "type": "manuscript", "label": "PMID 34721973 full text"}, {"id": "data:geo:GSE30219", "type": "dataset", "label": "GEO GSE30219"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34721973", "type": "paper", "label": "pmid:34721973"}, {"id": "source:pmid:34721973", "type": "manuscript", "label": "PMID 34721973 full text"}, {"id": "data:geo:GSE30219", "type": "dataset", "label": "GEO GSE30219"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34721973", "type": "extraction", "used": ["source:pmid:34721973"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30219", "type": "accession_resolution", "used": ["data:geo:GSE30219"], "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:34721973", "parent_hash": "sha256:1f190a0a5b71af6e5367cd2f1930a2e3b70983b9064b34c3bbeaca974804a945", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE30219 licence not read", "asset:data:geo:GSE30219 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", "asset:data:geo:GSE72094 licence not read", "asset:data:geo:GSE72094 not downloaded", "execution.not_run", "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": ["The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method."], "order_basis": "analysis_only", "id": "assay:1"}]}