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

Autor: Michl, Marlies, Taverna, Francesco, Woischke, Christine, Li, Pan, Klauschen, Frederick, Kirchner, Thomas, Heinemann, Volker, von Bergwelt-Baildon, Michael, Stahler, Arndt, Herold, Tobias Marcus, Jurinovic, Vindi, Engel, Jutta, Kumbrink, Jörg, Neumann, Jens
Zdroj: Clinical & Translational Oncology; Aug2024, Vol. 26 Issue 8, p1886-1895, 10p
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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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