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Our analysis revealed hepatic dysfunction promotes BC progression through five interconnected pathways: insulin resistance-driven IGF1-PI3K\/AKT activation, estrogen metabolism imbalance via CYP19A1\/ESR1, IL6-STAT3\/NLRP3-mediated inflammation, HMOX1\/APOE-dependent metabolic rewiring, and FAK-Src\/MMP9-regulated ECM remodeling. Key molecular mediators include nuclear receptors (ESR1), cytokines (IL-1\u03b2), growth factors (HGF), and receptor tyrosine kinases, with SPP1 and PTPN2 emerging as potential circulating biomarkers linking hepatic dysfunction to aggressive BC phenotypes. The crosstalk between hepatic dysfunction and BC is mediated by a network of proteins and pathways, offering potential targets for therapeutic intervention. Future research should focus on translational validation and personalized strategies for BC patients with comorbid liver conditions. This mechanistic insight may advance early diagnosis and precision treatment paradigms.<\/jats:p>","DOI":"10.1007\/s11427-025-3176-0","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:36:22Z","timestamp":1773707782000},"page":"1929-1949","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression"],"prefix":"10.1007","volume":"69","author":[{"given":"Gao","family":"Yuanze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Ganesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"3176_CR1","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.3390\/ijms19051308","volume":"19","author":"A Adamek","year":"2018","unstructured":"Adamek, A., and Kasprzak, A. 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