Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34419075", "kind": "science-record", "revision": 8, "content_hash": "sha256:1d847f8f0934249d3f9389f3b93f02bbecd45490a2e554906e6fd970db26384a", "created_at": "2026-11-01T15:41:48Z", "updated_at": "2026-11-01T22:47:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.", "doi": "10.1186/s12967-021-03031-w", "pmid": "34419075", "authors": ["Songhua Cai", "Xiaotong Guo", "Chujian Huang", "Youjun Deng", "Longde Du", "Wenyi Liu", "Chenglin Yang", "Hongbo Zhao", "Kai Ma", "Lixu Wang", "Jie He", "Zhentao Yu"], "journal": "Journal of translational medicine", "year": 2021, "abstract": "Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28-2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46-5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19-3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.", "claims": [{"id": "claim-method", "statement": "The differentially expressed genes (DEGs) involved in angiogenesis in the LUAD patients were identified with the “limma” R package (absolute log2-fold change (FC) > 1 and an adjusted P value < 0.05), in which we used the Benjamini-Hochberg (BH) method to obtain false discovery rate (FDR) as the adjusted P value.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34419075", "locator": "sections[3] \"Identification of differentially expressed genes (DEGs) and functional enrichment analysis between LUAD and nontumor tissues\" paragraph 2", "quote": "The differentially expressed genes (DEGs) involved in angiogenesis in the LUAD patients were identified with the “limma” R package (absolute log2-fold change (FC) > 1 and an adjusted P value < 0.05), in which we used the Benjamini-Hochberg (BH) method to obtain false discovery rate (FDR) as the adjusted P value."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data and material used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34419075", "locator": "sections[29] \"Availability of data and materials\" paragraph 2", "quote": "The data and material used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34419075"], "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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The cells were transfected with 50 nM COL5A2 siRNA or EPHB2 siRNA in ba", "enic gene prognostic model. Cell culture and siRNA administration The human LUAD cell lines, in", "The cells were transfected with 50 nM COL5A2 siRNA or EPHB2 siRNA in basic DMEM for 6–8 h and t", "transfected with 50 nM COL5A2 siRNA or EPHB2 siRNA in basic DMEM for 6–8 h and then changed to"], "order_basis": "paper_text_order:2636", "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": ["sas, VA, USA). The A549 and H1299 cells were cultured in DMEM (Gibco, NYC, USA) containing 10% fetal", "tration The human LUAD cell lines, including A549 cells and H1299 cells, were purchased from t", "e Collection (ATCC) (Manassas, VA, USA). The A549 and H1299 cells were cultured in DMEM (Gibco", "BS and 100 U/ml penicillin–streptomycin. The A549 and H1299 cells were treated with COL5A2 siR"], "order_basis": "paper_text_order:2694", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ssion of COL5A2 and EPHB2 in lung cancer, an immunohistochemistry assay was used to detect the levels of these", "2 in LUAD tissues and nontumor tissues. 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