Clinical M2 Macrophage-Related Genes Can Serve as a Reliable Predictor of Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35936688", "kind": "science-record", "revision": 5, "content_hash": "sha256:594a4d4dd4fe6c49bdd73ff56fe2da9932c59dadcf48bc46872ed349bf691763", "created_at": "2026-11-01T18:15:02Z", "updated_at": "2026-11-01T22:49:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Clinical M2 Macrophage-Related Genes Can Serve as a Reliable Predictor of Lung Adenocarcinoma.", "doi": "10.3389/fonc.2022.919899", "pmid": "35936688", "authors": ["Chaojie Xu", "Lishan Song", "Yubin Yang", "Yi Liu", "Dongchen Pei", "Jiabang Liu", "Jianhua Guo", "Nan Liu", "Xiaoyong Li", "Yuchen Liu", "Xuesong Li", "Lin Yao", "Zhengjun Kang"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Background: Numerous studies have found that infiltrating M2 macrophages play an important role in the tumor progression of lung adenocarcinoma (LUAD). However, the roles of M2 macrophage infiltration and M2 macrophage-related genes in immunotherapy and clinical outcomes remain obscure.\nMethods: Sample information was extracted from TCGA and GEO databases. The TIME landscape was revealed using the CIBERSORT algorithm. Weighted gene co-expression network analysis (WGCNA) was used to find M2 macrophage-related gene modules. Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out. Risk score (RS) was calculated, and all samples were divided into high-risk group (HRG) and low-risk group (LRG) according to the median RS. External validation of RS was performed using GSE68571 data information. Prognostic nomogram based on risk signatures and other clinical information were constructed and validated with calibration curves. Potential associations of tumor mutational burden (TMB) and risk signatures were analyzed. Finally, the potential association of risk signatures with chemotherapy efficacy was investigated using the pRRophetic algorithm.\nResults: Based on 504 samples extracted from TCGA database, 183 core genes were identified using WGCNA. Through a series of screening, two M2 macrophage-related genes (GRIA1 and CLEC3B) strongly correlated with LUAD prognosis were finally selected. RS was calculated, and prognostic risk nomogram including gender, age, T, N, M stage, clinical stage, and RS were constructed. The calibration curve shows that our constructed model has good performance. HRG patients were suitable for new ICI immunotherapy, while LRG was more suitable for CTLA4-immunosuppressive therapy alone. The half-maximal inhibitory concentrations (IC50) of the four chemotherapeutic drugs (metformin, cisplatin, paclitaxel, and gemcitabine) showed significant differences in HRG/LRG.\nConclusions: In conclusion, a comprehensive analysis of the role of M2 macrophages in tumor progression will help predict prognosis and facilitate the advancement of therapeutic techniques.", "claims": [{"id": "claim-method", "statement": "Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35936688", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35936688", "locator": "sections[31] \"Data Availability Statement\" paragraph 2", "quote": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A risk signature based on the M2 macrophage-related genes GRIA1 and CLEC3B was established as an independent prognostic indicator for LUAD and validated in the GSE68571 cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35936688", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through a series of screening, two M2 macrophage-related genes (GRIA1 and CLEC3B) strongly correlated with LUAD prognosis were finally selected."}, {"asset": "source:pmid:35936688", "locator": "sections[20] \"Validation of Risk Prognostic Features\" paragraph 2", "quote": "These results all consistently indicate that the M2 macrophage-related genes GRIA1 and CLEC3B have good predictive power for clinical outcomes, and the risk signature is an independent prognostic indicator for LUAD."}, {"asset": "source:pmid:35936688", "locator": "sections[20] \"Validation of Risk Prognostic Features\" paragraph 3", "quote": "Both internal validation with the TCGA-LUAD cohort and external validation with the GSE68571 cohort ( Figures 4D–F ) demonstrated a stable and robust prognostic value for this risk prognostic feature."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A risk signature based on the M2 macrophage-related genes GRIA1 and CLEC3B was established as an independent prognostic indicator for LUAD and validated in the GSE68571 cohort.", "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:35936688"], "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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