Integrated analysis of scRNA-seq and bulk RNA-seq identifies matrisome-related biomarkers for prognostic stratification and immune landscape in lung adenocarcinoma.

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Understanding the interplay between MRGs, the tumor microenvironment, and host immunity is critical for mechanistic insights. LUAD transcriptomic and clinical data were sourced from TCGA, GEO (GSE31210), and single-cell data (GSE189357). MRGs were analyzed via limma, with prognostic genes identified using univariate Cox. A LASSO-multivariate Cox model was built and validated using Kaplan-Meier, receiver operating characteristic, and external datasets. Functional enrichment (GO/KEGG/GSEA), immune infiltration (ssGSEA/ESTIMATE/CIBERSORT), tumor mutational burden, immunotherapy response, and drug sensitivity were assessed. Consensus clustering defined molecular subtypes. Single-cell analysis (Seurat/SCISSOR) identified risk-associated cells, with AUCell and CellChat evaluating activity and cell communication. A 7-gene risk model (ANGPTL4, C1QTNF6, CCL20, CLEC3B, FCN1, LAMA3, PRELP) stratified LUAD patients into distinct survival groups (area under the curve > 0.7). Low-risk patients showed higher immune infiltration, lower TIDE scores (suggesting better immunotherapy response), and reduced sensitivity to Axitinib/Gefitinib. Single-cell analysis implicated fibroblasts and myeloid cells in high-risk profiles, with activated MIF/TGF-β pathways. This integrated transcriptomic and single-cell model predicts LUAD prognosis and immune landscape, guiding personalized therapy.", "claims": [{"id": "claim-method", "statement": "MRGs were analyzed via limma, with prognostic genes identified using univariate Cox. A LASSO-multivariate Cox model was built and validated using Kaplan–Meier, receiver operating characteristic, and external datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41496514", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "MRGs were analyzed via limma, with prognostic genes identified using univariate Cox. 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The initial dataset comprised 583 samples, including 59 normal and 524 tumor samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 7-gene risk model (ANGPTL4, C1QTNF6, CCL20, CLEC3B, FCN1, LAMA3, PRELP) stratified LUAD patients into distinct survival groups (area under the curve > 0.7).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41496514", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A 7-gene risk model (ANGPTL4, C1QTNF6, CCL20, CLEC3B, FCN1, LAMA3, PRELP) stratified LUAD patients into distinct survival groups (area under the curve > 0.7)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 7-gene risk model (ANGPTL4, C1QTNF6, CCL20, CLEC3B, FCN1, LAMA3, PRELP) stratified LUAD patients into distinct survival groups (area under the curve > 0.7).", "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:41496514"], "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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