Mendelian Randomization and Bioinformatics Analysis Reveal the Potential Protective Role of Metformin in Primary Liver Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41189590", "kind": "science-record", "revision": 3, "content_hash": "sha256:17f77d663df55fd59975d30ddebf282673875cf083ad84377156cce9e4cd61d1", "created_at": "2026-11-01T20:31:13Z", "updated_at": "2026-11-01T22:14:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mendelian Randomization and Bioinformatics Analysis Reveal the Potential Protective Role of Metformin in Primary Liver Cancer.", "doi": "10.1002/fsn3.71156", "pmid": "41189590", "authors": ["Yongxin Ma", "Jiaojiao Qi", "Zhiqiang Chen", "Yubo Zhang", "Kejun Liu", "Jiaxin Suo", "Bendong Chen", "Yang Bu"], "journal": "Food science & nutrition", "year": 2025, "abstract": "Primary liver cancer (PLC) and metformin are not well understood to be associated. We conducted a Mendelian randomization (MR) analysis using genetic data from IEU OpenGWAS and FinnGen R10, with metformin as the exposure and PLC as the outcome. The inverse variance weighting (IVW) method was the primary analytical approach, with heterogeneity assessed by Cochran's Q test, pleiotropy by MR-Egger intercept, and outliers by MR-PRESSO. Bioinformatics analyses further explored potential mechanisms, including differential gene expression, protein-protein interactions (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune cell infiltration analysis, and drug sensitivity analysis. MR results demonstrated a significant association between metformin use and reduced risk of PLC (β = -5.6046, OR = 0.0037, p = 0.026), with a Benjamini-Hochberg false discovery rate (FDR) adjusted p value of 0.13. However, no causal effect was observed for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC). By cross-referencing transcriptome data from the GEO database GSE241466 with metformin-related gene loci, 34 overlapping genes were identified. Differentially expressed genes (DEGs) were filtered using |log2FC| > 0 and p < 0.05, with five hub genes (DDX52, KIF11, GCDH, MRPL45, and TICRR) being particularly prominent. Functional enrichment analysis revealed involvement in cGMP-PKG signaling and fatty acid metabolism pathways. Further validation with GEPIA2, TIMER, and TISCH showed correlations between these genes and immune infiltration, while GSCA-based drug sensitivity analysis suggested therapeutic relevance. In summary, these findings indicate that metformin may reduce PLC risk by modulating metabolic and immune-related pathways, supporting its potential value as an adjunct therapeutic agent. However, further validation through large-scale clinical and basic research is warranted.", "claims": [{"id": "claim-method", "statement": "Primary causal inference employed inverse‐variance weighted (IVW) regression with fixed effects, aggregating instrumental variables through inverse‐variance weighting.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41189590", "locator": "sections[6] \"MR Analysis and Statistical Analysis\" paragraph 2", "quote": "Primary causal inference employed inverse‐variance weighted (IVW) regression with fixed effects, aggregating instrumental variables through inverse‐variance weighting."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data used in this study are included in this paper or uploaded as Supporting Information, and public data are available on public platforms. No other unpublished data are available for this study. 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