Mendelian randomization and single-cell analysis reveal causal relationships between renal clear cell carcinoma, kidney fibrosis, and inflammatory factors.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40853443", "kind": "science-record", "revision": 2, "content_hash": "sha256:a4743027496eb7b8083b85051aaba255a0fc63faae451d00731a327ae32d4467", "created_at": "2026-11-01T20:30:57Z", "updated_at": "2026-11-01T21:35:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mendelian randomization and single-cell analysis reveal causal relationships between renal clear cell carcinoma, kidney fibrosis, and inflammatory factors.", "doi": "10.1007/s12672-025-03343-z", "pmid": "40853443", "authors": ["Xian Chen", "Hui Wang", "Qianqian Li", "Haiping Jia", "Tingting Ding", "Wentao Liu", "Jiansong Shen"], "journal": "Discover oncology", "year": 2025, "abstract": "BACKGROUND: Renal clear cell carcinoma (RCC) is the most common type of kidney cancer, and its relationship with kidney fibrosis and inflammatory responses has attracted considerable attention. However, whether causal relationships exist among these associations remains unclear, as traditional observational studies are susceptible to confounding factors. To evaluate causal relationships between kidney cancer, kidney fibrosis, and inflammatory factors using Mendelian randomization, and explore tumor microenvironment heterogeneity through single-cell analysis.\nMETHODS: Based on large-scale GWAS data, bidirectional Mendelian randomization analysis was performed to assess causal relationships between kidney cancer and kidney fibrosis, using MR Egger, inverse variance weighted (IVW), and weighted mode methods. Causal associations between kidney cancer and inflammatory factors including Axin-1, C-C motif chemokine 28, and interleukin-10 receptor subunit were analyzed. Single-cell RNA sequencing data from the GEO database (GSM4819725) was integrated for tumor microenvironment analysis.\nRESULTS: Bidirectional Mendelian randomization analysis revealed no significant causal relationship between kidney cancer and kidney fibrosis [kidney cancer→kidney fibrosis: IVW OR=0.992(95%CI: 0.913-1.077, P=0.842); kidney fibrosis→kidney cancer: IVW OR=0.922(95%CI: 0.824-1.030, P=0.151)]. However, significant positive causal associations were identified between kidney cancer and multiple inflammatory factors: Axin-1 levels [OR=1.448(95%CI: 1.107-1.894, P=0.007)], C-C motif chemokine 28 [OR=1.287(95%CI: 1.076-1.540, P=0.006)], and interleukin-10 receptor subunit [OR=1.135(95%CI: 1.032-1.248, P=0.009)]. Sensitivity analyses confirmed the robustness of results. Single-cell analysis revealed cellular heterogeneity in the tumor microenvironment, including various cell types such as immune cells, T cells, and NK cells, with pseudotime analysis demonstrating cell differentiation trajectories and dynamic gene expression changes.\nCONCLUSIONS: Mendelian randomization analysis provides genetic evidence for causal relationships between kidney cancer and inflammatory factors, while excluding direct causal associations between kidney cancer and kidney fibrosis.", "claims": [{"id": "claim-method", "statement": "This study employed a bidirectional two-sample Mendelian randomization design to assess causal relationships between renal clear cell carcinoma and kidney fibrosis as well as inflammatory factors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40853443", "locator": "sections[4] \"Mendelian randomization analysis methods\" paragraph 2", "quote": "This study employed a bidirectional two-sample Mendelian randomization design to assess causal relationships between renal clear cell carcinoma and kidney fibrosis as well as inflammatory factors."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that supported the fndings of this study are openly available in database (GSM4819725).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40853443", "locator": "sections[25] \"notes\" paragraph 1", "quote": "The data that supported the fndings of this study are openly available in database (GSM4819725)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bidirectional Mendelian randomization using large-scale GWAS data found no significant causal relationship between kidney cancer and kidney fibrosis, but significant positive causal associations between kidney cancer and Axin-1, C-C motif chemokine 28, and interleukin-10 receptor subunit.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Bidirectional Mendelian randomization analysis revealed no significant causal relationship between kidney cancer and kidney fibrosis [kidney cancer→kidney fibrosis: IVW OR=0.992(95%CI: 0.913-1.077, P=0.842); kidney fibrosis→kidney cancer: IVW OR=0.922(95%CI: 0.824-1.030, P=0.151)]."}, "evidence": [{"asset": "source:pmid:40853443", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Bidirectional Mendelian randomization analysis revealed no significant causal relationship between kidney cancer and kidney fibrosis [kidney cancer→kidney fibrosis: IVW OR=0.992(95%CI: 0.913-1.077, P=0.842); kidney fibrosis→kidney cancer: IVW OR=0.922(95%CI: 0.824-1.030, P=0.151)]."}, {"asset": "source:pmid:40853443", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "However, significant positive causal associations were identified between kidney cancer and multiple inflammatory factors: Axin-1 levels [OR=1.448(95%CI: 1.107-1.894, P=0.007)], C-C motif chemokine 28 [OR=1.287(95%CI: 1.076-1.540, P=0.006)], and interleukin-10 receptor subunit [OR=1.135(95%CI: 1.032-1.248, P=0.009)]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Bidirectional Mendelian randomization using large-scale GWAS data found no significant causal relationship between kidney cancer and kidney fibrosis, but significant positive causal associations between kidney cancer and Axin-1, C-C motif chemokine 28, and interleukin-10 receptor subunit.", "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:40853443"], "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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