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鉴定磷脂翻转酶 1 作为生物标志物并确定其对结直肠癌的预后价值。

Identification of phospholipid scramblase 1 as a biomarker and determination of its prognostic value for colorectal cancer.

机构信息

College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.

出版信息

Mol Med. 2011 Jan-Feb;17(1-2):41-7. doi: 10.2119/molmed.2010.00115. Epub 2010 Oct 5.

Abstract

The purpose of this study was to examine the expression of phospholipid scramblase 1 (PLSCR1) in tumor tissues and plasma specimens of patients with colorectal cancer (CRC), as well as analyze its association with clinical parameters. The expression levels of PLSCR1 protein in 104 matched CRC and adjacent normal tissue sections and 50 pairs of CRC tissue blocks were determined by use of immunohistochemical and Western blot analyses, respectively. To evaluate the diagnostic potential of PLSCR1, the plasma levels of PLSCR1 were investigated in 111 additional subjects (59 CRC patients and 52 healthy controls) by Western blot. PLSCR1 was overexpressed in malignant adenocarcinoma tissues compared with normal colorectal mucosa (P < 0.001). In addition, the plasma level of PLSCR1 was not only significantly elevated in CRC patients compared with healthy individuals (P < 0.001), but it was also substantially increased in early stage CRC (P < 0.001). Importantly, the overall sensitivity and specificity of PLSCR1 for CRC detection were 80% and 59.6%, respectively. The area under the ROC curve of PLSCR1 for CRC diagnosis is 0.75, which increases to 0.8 if combined with the measurement of carcinoembryonic antigen. Univariate analysis with the Cox regression model revealed that elevated PLSCR1 expression indicated a poor prognosis for CRC. This study showed that PLSCR1 protein levels were significantly elevated in both the cancer tissue and plasma of CRC patients. Moreover, the plasma levels of PLSCR1 were significantly elevated in patients with early stage CRC compared with healthy individuals, suggesting that PLSCR1 might be used as a noninvasive serological diagnostic and prognostic biomarker for CRC.

摘要

本研究旨在检测磷脂翻转酶 1(PLSCR1)在结直肠癌(CRC)患者肿瘤组织和血浆标本中的表达情况,并分析其与临床参数的关系。采用免疫组化和 Western blot 分析分别检测了 104 对配对的 CRC 及相邻正常组织切片中 PLSCR1 蛋白的表达水平,以及 50 对 CRC 组织块中 PLSCR1 蛋白的表达水平。为了评估 PLSCR1 的诊断潜能,通过 Western blot 分析对另外 111 例受试者(59 例 CRC 患者和 52 例健康对照者)的血浆 PLSCR1 水平进行了检测。与正常结直肠黏膜相比,恶性腺癌组织中 PLSCR1 呈过表达(P<0.001)。此外,CRC 患者的血浆 PLSCR1 水平不仅明显高于健康个体(P<0.001),而且在早期 CRC 中也显著升高(P<0.001)。重要的是,PLSCR1 对 CRC 检测的总敏感性和特异性分别为 80%和 59.6%。PLSCR1 用于 CRC 诊断的 ROC 曲线下面积为 0.75,如果与癌胚抗原的测定相结合,则增加到 0.8。Cox 回归模型的单因素分析显示,PLSCR1 表达升高预示 CRC 预后不良。本研究表明,CRC 患者的肿瘤组织和血浆中 PLSCR1 蛋白水平均显著升高。此外,与健康个体相比,早期 CRC 患者的血浆 PLSCR1 水平显著升高,提示 PLSCR1 可能作为一种非侵入性的血清学诊断和预后生物标志物用于 CRC。

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