Lower Expression of TWEAK is Associated with Poor Survival and Dysregulate TIICs in Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35707713", "kind": "science-record", "revision": 5, "content_hash": "sha256:cae666ef17f275f809d1c6658223e0346e982fa8456ead56f1a2e6ae64ae090c", "created_at": "2026-11-01T18:14:40Z", "updated_at": "2026-11-01T22:49:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Lower Expression of TWEAK is Associated with Poor Survival and Dysregulate TIICs in Lung Adenocarcinoma.", "doi": "10.1155/2022/8661423", "pmid": "35707713", "authors": ["Zhengxi He", "Sai Wang", "Jinchun Wu", "Yangchun Xie", "Bin Li"], "journal": "Disease markers", "year": 2022, "abstract": "Background: Lung cancer remains the leading cause of cancer death worldwide, and the most subtype is lung adenocarcinoma (LUAD). Tumor-infiltrating immune cells (TIICs) greatly impact the prognosis of LUAD. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), signal via its receptor fibroblast growth factor-inducible 14 (Fn14), dysregulates immune cell recruitment within tumor environment, thus promoting the progression of autoimmune diseases and cancer. We aimed to explore its role in LUAD.\nMethods: The expression level of TWEAK was explored in Tumor Immune Estimation Resource 2.0 (TIMER2.0) and Oncomine databases. The Tumor Immune Dysfunction and Exclusion (TIDE) and Lung Cancer Explorer (LCE) databases were applied to evaluate the survival in correlation to TWEAK expression. TIICs were assessed with TIMER2.0 and TIDE datasets. The expression of TWEAK protein was detected in LUAD cell lines and also in tissue samples from LUAD patients via western blotting or combination with immunochemistry.\nResults: Our results showed that TWEAK was downregulated in LUAD tumors compared to normal tissues in TIMER2.0, Oncomine, cell lines, and clinical specimens. Poor survival was uncovered in lower TWEAK expression of LUAD patients in LCE (meta - HR = 0.84 [95% CI, 0.76-0.92]) and TCGA (Continuous Z = -1.97, p = 0.0486) and GSE13213@PRECOG (Continuous Z = -4.25, p = 2.12e - 5) in TIDE. Multiple tumor-infiltrating immune cells (TIICs) were found closely correlated with TWEAK expression in LUAD, especially hematopoietic stem cell (Rho = 0.505, p = 2.78e - 33), common lymphoid progenitor (Rho = -0.504, p = 3.79e - 33), and myeloid-derived suppressor cells (MDSCs) (Rho = -0.615, p = 1.36e - 52).\nConclusion: Lower level of TWEAK was linked with poor survival and aberrant recruitment and phenotype of TIICs in LUAD, which might motivate immune escape and weaken the effects of immunotherapy.", "claims": [{"id": "claim-method", "statement": "The expression of TWEAK was calculated by the Wilcoxon test, and the purity-adjusted Rho between TWEAK and TIICs was computed by Spearman's correlation coefficient in TIMER2.0.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35707713", "locator": "sections[10] \"2.8. Statistical Analysis\" paragraph 2", "quote": "The expression of TWEAK was calculated by the Wilcoxon test, and the purity-adjusted Rho between TWEAK and TIICs was computed by Spearman's correlation coefficient in TIMER2.0."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding authors upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35707713", "locator": "sections[20] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding authors upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Lower TWEAK expression was associated with poor overall survival in patients with lung adenocarcinoma.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Poor survival was uncovered in lower TWEAK expression of LUAD patients in LCE (meta − HR = 0.84 [95% CI, 0.76-0.92]) and TCGA (Continuous Z = −1.97, p = 0.0486) and GSE13213@PRECOG (Continuous Z = −4.25, p = 2.12e − 5) in TIDE."}, "evidence": [{"asset": "source:pmid:35707713", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Poor survival was uncovered in lower TWEAK expression of LUAD patients in LCE (meta − HR = 0.84 [95% CI, 0.76-0.92]) and TCGA (Continuous Z = −1.97, p = 0.0486) and GSE13213@PRECOG (Continuous Z = −4.25, p = 2.12e − 5) in TIDE."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Lower TWEAK expression was associated with poor overall survival in patients with lung adenocarcinoma.", "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:35707713"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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