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Based on previous studies, we suggested that TAM\u2010mediated sex\u2010determining region Y\u2010box 9 (SOX9) signal might enhance HB progression. The present study investigated the significance of the SOX9 signal in HB and examined the mechanisms underlying cell\u2013cell interactions between tumour cells and TAMs. Co\u2010culture with human monocyte\u2010derived macrophages increased SOX9 expression in HB cell lines. Immunohistochemical analysis of HB samples revealed a positive correlation between SOX9 expression and TAM infiltration, and SOX9 expression was predominantly observed in the embryonal subtype. Increased SOX9 expression was associated with shorter 5\u2010year recurrence\u2010free and overall survival. Yes\u2010associated protein (YAP)\/transcriptional co\u2010activator with PDZ\u2010binding motif (TAZ) signalling was found to be involved in macrophage\u2010induced SOX9 upregulation. The Wnt\/\u03b2\u2010catenin pathway was also activated by co\u2010culture with macrophages and appeared to be upregulated by SOX9 expression. In summary, SOX9 was identified as a poor prognostic factor in HB, with expression enhanced by macrophage\u2010derived factors. The YAP\/TAZ and Wnt\/\u03b2\u2010catenin pathways are critical for cell\u2013cell communication and are linked to SOX9 overexpression. \u00a9 2026 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.70110","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:04:57Z","timestamp":1787821497000},"page":"396-407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aberrant\n                    <scp>SOX9<\/scp>\n                    expression mediated by protumour macrophages predicts poorer clinical outcomes in hepatoblastoma"],"prefix":"10.1002","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-2676","authenticated-orcid":false,"given":"Hiroki","family":"Hirao","sequence":"first","affiliation":[{"name":"Department of Cell Pathology, Graduate School of Medical Sciences Kumamoto University  Kumamoto Japan"},{"name":"Department of 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