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.
Clin Transl Oncol. 2024 Aug;26(8):1886-1895. doi: 10.1007/s12094-024-03408-5. Epub 2024 Mar 17.
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.
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.
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).
The NFAT5, ACVR1C and SMC3 gene expression signature is associated with colorectal BM. Future studies should further investigate the importance of this biomarker signature.
结直肠癌（CRC）脑转移（BM）是一种罕见的预后不良的疾病。除（K）RAS 状态和肺及骨转移外，尚无生物标志物可用于识别有风险的患者。本研究旨在确定与结直肠脑转移相关的基因表达特征。
形成了三组患者：1. 伴脑转移的 CRC（BRA），2. 单纯肝转移（HEP），3. 无转移疾病（M0）。从原发肿瘤中提取 RNA，使用 NanoString 面板（770 个基因）测量 mRNA 表达。在验证队列中通过 qPCR 进行表达验证。进行了包括多变量逻辑回归和随后的接收者操作特征（ROC）分析的统计分析。
EMILIN3、MTA1、SV2B、TMPRSS6、ACVR1C、NFAT5 和 SMC3 在 BRA 和 HEP/M0 组中差异表达。在验证队列中，证实了差异 NFAT5、ACVR1C 和 SMC3 的表达。与 HEP/M0 组相比，BRA 患者的 NFAT5 水平最高（总体 p=0.02）。在 BRA 组中观察到更高频率的 ACVR1C 高表达（42.9%），而在 HEP（0%）和 M0（7.1%）组中则较低（总体 p=0.01）。仅在 BRA 组中可检测到 SMC3 的高表达（总体 p=0.003）。只有 BM 患者表现出 NFAT5、ACVR1C 或 SMC3 以及所有三种基因的联合高表达。ROC 分析显示该三基因对脑转移有较好的预测效果（曲线下面积（AUC）=0.78）。
NFAT5、ACVR1C 和 SMC3 基因表达特征与结直肠脑转移相关。未来的研究应进一步探讨该生物标志物特征的重要性。
