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pmid:36275753
Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma.
Liangming Zhang · Biwang Jiang · Zhuxiang Lan · Chaomian Yang · Yien Yao · Jie Lin · Qiu Wei
Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.983570
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.\nMethods: We adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.\nResults: Two immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients' prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.\nConclusion: Altogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.", "claims": [{"id": "claim-method", "statement": "The co-expression network of DEGs shared by four datasets was constructed via the weighted gene correlation network analysis (WGCNA) package (17).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36275753", "locator": "sections[5] \"Weighted gene correlation network analysis\" paragraph 2", "quote": "The co-expression network of DEGs shared by four datasets was constructed via the weighted gene correlation network analysis (WGCNA) package (17)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE32863", "GSE43458", "GSE75037", "GSE72094"], "resolved_accessions": ["GSE32863", "GSE43458", "GSE75037", "GSE72094"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE32863, GSE43458, GSE75037, 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": [], "assets": ["source:pmid:36275753", "data:geo:GSE32863"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE32863"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:12:41Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11879, "completion_tokens": 2115, "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:36275753", "type": "paper", "label": "pmid:36275753"}, {"id": "source:pmid:36275753", "type": "manuscript", "label": "PMID 36275753 full text"}, {"id": "data:geo:GSE32863", "type": "dataset", "label": "GEO GSE32863"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36275753", "type": "paper", "label": "pmid:36275753"}, {"id": "source:pmid:36275753", "type": "manuscript", "label": "PMID 36275753 full text"}, {"id": "data:geo:GSE32863", "type": "dataset", "label": "GEO GSE32863"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36275753", "type": "extraction", "used": ["source:pmid:36275753"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE32863", "type": "accession_resolution", "used": ["data:geo:GSE32863"], "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:36275753", "parent_hash": "sha256:2b470d0039e4dfba96bb23e3c2fa3727dd659ad8f3b45e1dc082fe354640aa5a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE32863 licence not read", "asset:data:geo:GSE32863 not downloaded", "asset:data:geo:GSE43458 licence not read", "asset:data:geo:GSE43458 not downloaded", "asset:data:geo:GSE72094 licence not read", "asset:data:geo:GSE72094 not downloaded", "asset:data:geo:GSE75037 licence not read", "asset:data:geo:GSE75037 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Materials and methods Cell culture and transfection Human lung normal epithelial cell line (BEAS", "of polybrene for 12 h. NCI-H1975 cells were transfected with 10 nmol/L short interfering RNAs (siRNA", "was adopted to examine EXO1 expression after transfection. Statistical analysis Data were expressed as", "ghai, China) or a scrambled negative control siRNA (siRNA NC; Hanyin) via Lipofectamine 2000 (I"], "order_basis": "paper_text_order:1925", "id": "assay:1"}, {"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": [") and LUAD cell lines (NCI-H1975, NCI-H1395, A549, and PC9) were cultivated in Roswell Park Me", ") following the manufacturer’s instructions. A549 cells were treated with pLenti-CMV-GFP-Puro-"], "order_basis": "paper_text_order:2024", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["NA5, 5′-CCATTTCACCACCCACTTT-3′. Quantitative real-time PCR was adopted to examine EXO1 expression after"], "order_basis": "paper_text_order:3061", "id": "assay:3"}, {"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": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}