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pmid:33976960
Identification of a novel autophagy signature for predicting survival in patients with lung adenocarcinoma.
Jin Duan · Youming Lei · Guoli Lv · Yinqiang Liu · Wei Zhao · Qingmei Yang · Xiaona Su · Zhijian Song · Leilei Lu · Yunfei Shi
PeerJ · 2021 doi:10.7717/peerj.11074
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Complete file
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In this study, we aimed to identify autophagy-related genes (ARGs) and develop an LUAD prognostic signature.\nMETHODS: In this study, we obtained ARGs from three databases and downloaded gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used TCGA-LUAD (n = 490) for a training and testing dataset, and GSE50081 (n = 127) as the external validation dataset.The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature. We performed gene set enrichment analysis (GSEA) and immune cell analysis between the high- and low-risk groups. A nomogram was built to guide the individual treatment for LUAD patients.\nRESULTS: We identified a total of 83 differentially expressed ARGs (DEARGs) from the TCGA-LUAD dataset, including 33 upregulated DEARGs and 50 downregulated DEARGs, both with thresholds of adjusted P < 0.05 and |Fold change| > 1.5. Using LASSO and multivariate Cox regression analyses, we identified 10 ARGs that we used to build a prognostic signature with areas under the curve (AUCs) of 0.705, 0.715, and 0.778 at 1, 3, and 5 years, respectively. Using the risk score formula, the LUAD patients were divided into low- or high-risk groups. Our GSEA results suggested that the low-risk group were enriched in metabolism and immune-related pathways, while the high-risk group was involved in tumorigenesis and tumor progression pathways. Immune cell analysis revealed that, when compared to the high-risk group, the low-risk group had a lower cell fraction of M0- and M1- macrophages, and higher CD4 and PD-L1 expression levels.\nCONCLUSION: Our identified robust signature may provide novel insight into underlying autophagy mechanisms as well as therapeutic strategies for LUAD treatment.", "claims": [{"id": "claim-method", "statement": "The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33976960", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nData are available at the Gene Expression Omnibus (GEO) database: GSE50081. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:33976960", "data:geo:GSE50081", "asset:table:pmid:33976960:1", "asset:table:pmid:33976960:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE50081"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:29:50Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 36493, "completion_tokens": 1374, "cached_tokens": 784}}, "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:33976960", "type": "paper", "label": "pmid:33976960"}, {"id": "source:pmid:33976960", "type": "manuscript", "label": "PMID 33976960 full text"}, {"id": "data:geo:GSE50081", "type": "dataset", "label": "GEO GSE50081"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33976960", "type": "paper", "label": "pmid:33976960"}, {"id": "source:pmid:33976960", "type": "manuscript", "label": "PMID 33976960 full text"}, {"id": "data:geo:GSE50081", "type": "dataset", "label": "GEO GSE50081"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33976960", "type": "extraction", "used": ["source:pmid:33976960"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE50081", "type": "accession_resolution", "used": ["data:geo:GSE50081"], "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:33976960", "parent_hash": "sha256:b0fcdd19b19edc99b9fb05ec108b16a65c62b543a3a7e85df7ec9b5a53999946", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE50081 licence not read", "asset:data:geo:GSE50081 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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 least absolute shrinkage and selection operator (LASSO) Cox and multivariate Cox regression models were used to generate an autophagy-related signature."], "order_basis": "analysis_only", "id": "assay:1"}]}