Identification of a gene expression signature associated with brain metastasis in colorectal cancer.

Autor: Michl M; Department of Medicine III, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany.; Department of Haematology and Oncology, Comprehensive Cancer Center Munich, Ludwig-Maximilian-University of Munich, Munich, Germany., Taverna F; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany., Woischke C; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany., Li P; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany., Klauschen F; Department of Haematology and Oncology, Comprehensive Cancer Center Munich, Ludwig-Maximilian-University of Munich, Munich, Germany.; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany., Kirchner T; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany., Heinemann V; Department of Medicine III, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany.; Department of Haematology and Oncology, Comprehensive Cancer Center Munich, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany., von Bergwelt-Baildon M; Department of Medicine III, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany.; Department of Haematology and Oncology, Comprehensive Cancer Center Munich, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany., Stahler A; Department of Hematology, Oncology, and Tumorimmunology, Corporate Member of Freie Universitaet Berlin and Humbolt-Universitaet zu Berlin, Charité - Universitaetsmedizin Berlin, Berlin, Germany., Herold TM; Department of Medicine III, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany., Jurinovic V; Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilian-University of Munich, Munich, Germany., Engel J; Munich Cancer Registry (MCR), Ludwig-Maximilian-University of Munich, Munich, Germany., Kumbrink J; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany. Joerg.Kumbrink@med.uni-muenchen.de.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany. Joerg.Kumbrink@med.uni-muenchen.de., Neumann J; Institute of Pathology, Faculty of Medicine, Ludwig-Maximilian-University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico [Clin Transl Oncol] 2024 Aug; Vol. 26 (8), pp. 1886-1895. Date of Electronic Publication: 2024 Mar 17.
DOI: 10.1007/s12094-024-03408-5
Abstrakt: Purpose: Brain metastasis (BM) in colorectal cancer (CRC) is a rare event with poor prognosis. 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.
Methods: 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.
Results: 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 p = 0.02). High ACVR1C expression was observed more frequently in the BRA group (42.9%) than in HEP (0%) and M0 (7.1%) groups (global p = 0.01). High SMC3 expressions were only detectable in the BRA group (global p = 0.003). 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)  = 0.78).
Conclusions: The NFAT5, ACVR1C and SMC3 gene expression signature is associated with colorectal BM. Future studies should further investigate the importance of this biomarker signature.
(© 2024. The Author(s).)
Databáze: MEDLINE
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