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the 5th PIA, integrated into France 2030 with the reference","award":["ANR-21-RHUS-0003"],"award-info":[{"award-number":["ANR-21-RHUS-0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. Methods: Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry. We further assessed the clinico-pathological associations and prognostic value of our signature in the COAD-TCGA independent cohort. Results: We identified a significantly different distribution of Consensus Molecular Subtypes between CRC-Liver and CRC-peritoneum groups. A transcriptomic signature based on 61 genes discriminated between liver and peritoneal metastatic routes. GSEA showed a higher expression of immune response and epithelial invasion pathways in CRC-Peritoneum samples and activation of proliferation and metabolic pathways in CRC-Liver samples. The biological relevance of RNA-Seq results was validated by the immunohistochemical expression of three significantly differentially expressed genes (ACE2, CLDN18 and DUSP4) in our signature. In silico analysis of the COAD-TCGA showed that the CRC-Peritoneum signature was associated with negative prognostic factors and poor overall and disease-free survivals. Conclusions: CRC primary tumors spreading to the liver and peritoneum display significantly different transcriptomic profiles. The implementation of this signature in clinical practice could contribute to identify new therapeutic targets for stage IV CRC and to define individualized follow-up programs in stage II-III CRC.<\/jats:p>","DOI":"10.3390\/cancers15174418","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:24:30Z","timestamp":1693823070000},"page":"4418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9807-4021","authenticated-orcid":false,"given":"Maximiliano","family":"Gelli","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France"},{"name":"Gustave Roussy, D\u00e9partement de Anesth\u00e9sie, Chirurgie et Interventionnel, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-2524","authenticated-orcid":false,"given":"Christophe","family":"Desterke","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Saclay, INSERM, Mod\u00e8les de Cellules Souches Malignes et Th\u00e9rapeutiques (UMR1310), F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-4905","authenticated-orcid":false,"given":"Mohamed Amine","family":"Bani","sequence":"additional","affiliation":[{"name":"Gustave Roussy, D\u00e9partement de Biologie et Pathologie M\u00e9dicale, F-94805 Villejuif, France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS, Inserm, US23, UMS3655, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Boige","sequence":"additional","affiliation":[{"name":"Gustave Roussy, D\u00e9partement de M\u00e9decine Oncologique, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Fert\u00e9","sequence":"additional","affiliation":[{"name":"Gustave Roussy, D\u00e9partement de M\u00e9decine Oncologique, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Dartigues","sequence":"additional","affiliation":[{"name":"Gustave Roussy, D\u00e9partement de Biologie et Pathologie M\u00e9dicale, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien","family":"Job","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CNRS, Inserm, US23, UMS3655, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-2534","authenticated-orcid":false,"given":"Geraldine","family":"Perkins","sequence":"additional","affiliation":[{"name":"Institut du Cancer Paris CARPEM, AP-HP, AP-HP Centre, Department of Hepatogastroenterology and Digestive Oncology, H\u00f4pital Europ\u00e9en Georges Pompidou, 20 Rue Leblanc, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-5459","authenticated-orcid":false,"given":"Pierre","family":"Laurent-Puig","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, USPC, Universit\u00e9 Paris Descartes, Universit\u00e9 Paris Diderot, Centre de Recherche des Cordeliers, INSERM, CNRS, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Go\u00e9r\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France"},{"name":"Gustave Roussy, D\u00e9partement de Anesth\u00e9sie, Chirurgie et Interventionnel, F-94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques R. 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