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Apart from (K)RAS status and lung and bone metastasis no biomarkers exist to identify patients at risk. This study aimed to identify a gene expression signature associated with colorectal BM.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Three patient groups were formed: 1. CRC with brain metastasis (BRA), 2. exclusive liver metastasis (HEP) and, 3. non-metastatic disease (M0). RNA was extracted from primary tumors and mRNA expression was measured using a NanoString Panel (770 genes). Expression was confirmed by qPCR in a validation cohort. Statistical analyses including multivariate logistic regression followed by receiver operating characteristic (ROC) analysis were performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>EMILIN3, MTA1, SV2B, TMPRSS6, ACVR1C, NFAT5 and SMC3 were differentially expressed in BRA and HEP\/M0 groups. In the validation cohort, differential NFAT5, ACVR1C and SMC3 expressions were confirmed. BRA patients showed highest NFAT5 levels compared to HEP\/M0 groups (global <jats:italic>p<\/jats:italic>\u2009=\u20090.02). High ACVR1C expression was observed more frequently in the BRA group (42.9%) than in HEP (0%) and M0 (7.1%) groups (global <jats:italic>p<\/jats:italic>\u2009=\u20090.01). High SMC3 expressions were only detectable in the BRA group (global <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Only patients with BM showed a combined high expression of NFAT5, ACVR1C or SMC3 as well as of all three genes. ROC analysis revealed a good prediction of brain metastasis by the three genes (area under the curve (AUC)\u2009 =\u20090.78).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The NFAT5, ACVR1C and SMC3 gene expression signature is associated with colorectal BM. Future studies should further investigate the importance of this biomarker signature.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12094-024-03408-5","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T09:12:37Z","timestamp":1711962757000},"page":"1886-1895","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of a gene expression signature associated with brain metastasis in colorectal cancer"],"prefix":"10.1007","volume":"26","author":[{"given":"Marlies","family":"Michl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Taverna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Woischke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Klauschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kirchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"von Bergwelt-Baildon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Stahler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias Marcus","family":"Herold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vindi","family":"Jurinovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4105","authenticated-orcid":false,"given":"J\u00f6rg","family":"Kumbrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"3408_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41698-018-0047-0","volume":"2","author":"W Chen","year":"2018","unstructured":"Chen W, Hoffmann AD, Liu H, Liu X. 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However, apart from the submitted work MM received honoraria for talks and advisory boards by SIRTeX, Roche, AstraZeneca, Novartis, Merck, Sanofi, Lilly and MSD, travel expenses by SIRTeX, Amgen, Sobi and Merck. AS received honoraria for Advisory Roles from BMS and NovoCure, honoraria for talks from Roche, Taiho Pharmaceutical, Servier and expenses for travel and accommodations from Roche, Merck KGaA, Amgen, Pfizer and Lilly Oncology. JN received honoraria for talks and advisory boards by Roche, Novartis, Pfizer, MSD, BMS, Falk and Pierre Fabre. VH received honoraria for talks, advisory boards and travel expenses by Merck, Amgen, Roche, Takeda, Servier, Pierre Fabre, Taiho, Lilly Oncology, Servier, Sanofi and Bayer Pharmaceuticals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ethics approval and content was obtained from the local ethics committee (Approval Number 18-105). The study was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Informed consent was obtained from all subjects involved in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}