Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, Level 8, St James's University Hospital, Leeds LS9 7TF, UK.
Breast Cancer Res Treat. 2010 Jun;121(3):555-63. doi: 10.1007/s10549-009-0500-4. Epub 2009 Aug 8.
CUB and SUSHI multiple domain protein 1 (CSMD1) is a candidate tumour suppressor gene that maps to chromosome 8p23, a region deleted in many tumour types including 50% of breast cancers. CSMD1 has homologies to proteins implicated in carcinogenesis. We aimed to study the expression pattern of the CSMD1 protein and evaluate its prognostic importance in invasive ductal carcinoma (IDC). An anti-CSMD1 antibody was developed and validated. The expression pattern of CSMD1 in normal breast and IDC samples was investigated by immunohistochemistry in 275 patients. Univariate and multivariate Cox regression analyses were performed. In normal breast duct epithelial cells, luminal, membranous and cytoplasmic CSMD1 staining was identified. Reduced expression of CSMD1 was detected in 79/275 (28.7%) of IDC cases. Low CSMD1 expression was significantly associated with high tumour grade (P = 0.003). CSMD1 expression was associated with overall survival (OS; HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not with disease-free survival (DFS; HR = 0.81, 95%CI: 0.46-1.43, P = 0.48). Multivariate analysis showed that CSMD1, together with Nottingham Prognostic Index, was considered an independent predictor of OS (HR = 0.607, 95%CI: 0.4-0.91, P = 0.018) but not DFS (HR = 0.84, 95%CI: 0.46-1.5, P = 0.573). Reduction of CSMD1 expression was significantly associated with high tumour grade and decreased OS. Therefore, our results support the idea that CSMD1 is a tumour suppressor gene and suggest its possible use as a new prognostic biomarker. The membrane expression pattern of CSMD1 suggests that it may be a receptor or co-receptor involved in the process of signal transduction.
CUB 和 Sushi 多结构域蛋白 1（CSMD1）是一种候选肿瘤抑制基因，定位于染色体 8p23，该区域在多种肿瘤类型中缺失，包括 50%的乳腺癌。CSMD1 与参与致癌作用的蛋白质具有同源性。我们旨在研究 CSMD1 蛋白的表达模式，并评估其在浸润性导管癌（IDC）中的预后意义。开发并验证了抗 CSMD1 抗体。在 275 例患者中，通过免疫组织化学研究了 CSMD1 蛋白在正常乳腺和 IDC 样本中的表达模式。进行了单变量和多变量 Cox 回归分析。在正常乳腺导管上皮细胞中，发现了腔、膜和细胞质 CSMD1 染色。在 275 例 IDC 病例中，检测到 79 例（28.7%）CSMD1 表达降低。低 CSMD1 表达与高肿瘤分级显著相关（P=0.003）。CSMD1 表达与总生存（OS；HR=0.607，95%CI：0.4-0.91，P=0.018）相关，但与无病生存（DFS；HR=0.81，95%CI：0.46-1.43，P=0.48）无关。多变量分析显示，CSMD1 与诺丁汉预后指数一起被认为是 OS 的独立预测因子（HR=0.607，95%CI：0.4-0.91，P=0.018），但不是 DFS（HR=0.84，95%CI：0.46-1.5，P=0.573）。CSMD1 表达降低与高肿瘤分级和 OS 降低显著相关。因此，我们的结果支持 CSMD1 是一种肿瘤抑制基因的观点，并表明其可能作为新的预后生物标志物。CSMD1 的膜表达模式表明，它可能是一种参与信号转导过程的受体或共受体。
