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鉴定内皮细胞特异性分子-1 作为结直肠癌的潜在血清标志物。

Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer.

机构信息

Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

出版信息

Cancer Sci. 2010 Oct;101(10):2248-53. doi: 10.1111/j.1349-7006.2010.01665.x. Epub 2010 Jul 30.

Abstract

No ideal serum markers for screening colorectal cancer (CRC) have been identified. The aim of this study was to determine the usefulness of endothelial cell-specific molecule-1 (ESM-1) as a serum marker for CRC. Illumina microarray was carried out to search CRC-related biomarkers. cDNA microarray detected that ESM-1 was one of the overexpressed genes in CRC. Overexpression of ESM-1 mRNA was confirmed in tissues of CRC by RT-PCR and real-time PCR. Immunohistochemical staining showed strong expression of ESM-1 in the cytoplasm of tumor cells. Overexpression of ESM-1 in human serum with CRC was found by Western blot analysis. For quantitative analysis of ESM-1 in serum, we determined the ESM-1 levels in serum specimens using an ELISA kit. We showed that the ESM-1 levels in the serum of patients with CRC were significantly elevated (70.1 ± 29.7 pg/mL) compared to healthy subjects (29.7 ± 14.9 pg/mL). The accuracy, sensitivity, and specificity of ESM-1 for CRC were 0.94, 99%, and 73%, respectively, by receiver operating characteristics curve analysis. The positive predictive value and negative predictive value were 63% and 95%, respectively. The likelihood ratios of a positive or negative test result were 73 and 0.27, respectively. When analyzed with a Cox regression model, a higher serum ESM-1 level (≥76.0 pg/mL) was correlated with poor prognosis. This study suggests that expression of ESM-1 is increased in tissue and serum of CRC patients and that ESM-1 can be used as a potential serum marker for the early detection of CRC.

摘要

尚未发现用于筛查结直肠癌 (CRC) 的理想血清标志物。本研究旨在确定内皮细胞特异性分子-1 (ESM-1) 作为 CRC 血清标志物的有用性。进行了 Illumina 微阵列以搜索与 CRC 相关的生物标志物。cDNA 微阵列检测到 ESM-1 是 CRC 中过度表达的基因之一。通过 RT-PCR 和实时 PCR 证实了 ESM-1 mRNA 在 CRC 组织中的过表达。免疫组织化学染色显示肿瘤细胞细胞质中 ESM-1 表达强烈。Western blot 分析发现 CRC 患者血清中 ESM-1 过表达。为了定量分析血清中的 ESM-1,我们使用 ELISA 试剂盒测定了血清标本中的 ESM-1 水平。我们表明,CRC 患者血清中的 ESM-1 水平明显升高(70.1 ± 29.7 pg/mL),与健康受试者(29.7 ± 14.9 pg/mL)相比。通过受试者工作特征曲线分析,ESM-1 对 CRC 的准确性、灵敏度和特异性分别为 0.94、99%和 73%。阳性预测值和阴性预测值分别为 63%和 95%。阳性或阴性检测结果的似然比分别为 73 和 0.27。当用 Cox 回归模型分析时,较高的血清 ESM-1 水平(≥76.0 pg/mL)与预后不良相关。本研究表明,ESM-1 在 CRC 患者的组织和血清中表达增加,ESM-1 可作为 CRC 早期检测的潜在血清标志物。

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