{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:15:09Z","timestamp":1788434109050,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010109","name":"Medical University of Graz","doi-asserted-by":"publisher","award":["8151"],"award-info":[{"award-number":["8151"]}],"id":[{"id":"10.13039\/501100010109","id-type":"DOI","asserted-by":"publisher"}]},{"award":["8151"],"award-info":[{"award-number":["8151"]}],"id":[{"id":"https:\/\/ror.org\/02n0bts35","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background &amp; Aims: Signaling within the tumor microenvironment (TME) emerges from dynamic crosstalk among cancer cells, host tissues, and the microbiome. Orthotopic and ectopic xenograft models are widely used in preclinical liver cancer research, yet it remains unclear to what extent tumor location shapes systemic host responses and gut\u2013liver communication. We therefore investigated how anatomical context influences host transcriptomes and spatially resolved intestinal microbial ecosystems in hepatoblastoma (HB). Methods: We integrated bacterial\/archaeal ecology with host and xenograft transcriptomes in orthotopic versus ectopic hepatoblastoma xenografts in male athymic CAnN.Cg-Foxn1nu\/Crl mice. Single-sample GSEA, sparsity-aware networks, and DIABLO multi-block integration mapped pathway-level coordination across intestinal segments, stool, secondary lymphoid organs, livers, and tumors. Results: Tumor localization was associated with compartment-specific differences in host signaling, with the mesenteric lymph node and liver showing prominent shifts in TNFA\/NF-\u03baB, hypoxia, unfolded protein response, xenobiotic metabolism, mTORC1, KRAS, epithelial\u2013mesenchymal transition, and MYC\/E2F cell-cycle axes. Archaea exhibited pronounced, niche-specific signatures that showed positive correlations with proliferative and inflammatory Hallmarks and negative correlations with interferon pathways. Multi-omics integration (r \u2265 0.85) indicated coordinated variation linking specific microbial families to host and tumor programs and positioned the xenograft block as a hub connecting EMT, mTORC1, and angiogenesis to defined archaeal and bacterial taxa. Conclusions: Tumor topography remodels TME signaling through compartment-dependent host\u2013microbiome\u2013tumor crosstalk, with archaeal domains emerging as salient correlates of proliferative and stress-response networks. These findings provide a systems framework and testable hypotheses for therapeutic modulation of TME signaling via interkingdom interactions.<\/jats:p>","DOI":"10.3390\/cancers18172854","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"2854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Topography Remodels TME Signalling via Compartment-Specific Host\u2013Microbiome\u2013Tumor Crosstalk in Hepatoblastoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-7916","authenticated-orcid":false,"given":"Beate","family":"Oberm\u00fcller","sequence":"first","affiliation":[{"name":"Department of Paediatric and Adolescent Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Sabine","family":"Oberm\u00fcller","sequence":"additional","affiliation":[{"name":"HEALTH\u2014Institute for Biomedical Research and Technologies, Joanneum Research Forschungsgesellschaft mbH, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Karin","family":"Wagner","sequence":"additional","affiliation":[{"name":"Center for Medical Research, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-0613","authenticated-orcid":false,"given":"Maximilian","family":"Nepel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-596X","authenticated-orcid":false,"given":"Holger","family":"Till","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4770-3144","authenticated-orcid":false,"given":"Georg","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-7560","authenticated-orcid":false,"given":"Bettina","family":"Leber","sequence":"additional","affiliation":[{"name":"Division of General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/cncr.33319","article-title":"Pediatric hepatic cancer incidence and survival: 30-year trends in Ontario, Canada; 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