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血清糖组学分析:卵巢癌潜在的新型生物标志物?

Glycomics analysis of serum: a potential new biomarker for ovarian cancer?

作者信息

Leiserowitz G S, Lebrilla C, Miyamoto S, An H J, Duong H, Kirmiz C, Li B, Liu H, Lam K S

机构信息

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, UC Davis Medical Center, Sacramento, California, USA.

出版信息

Int J Gynecol Cancer. 2008 May-Jun;18(3):470-5. doi: 10.1111/j.1525-1438.2007.01028.x. Epub 2007 Jul 26.

Abstract

We recently reported the use of matrix-assisted laser desorption ionization (MALDI) Fourier transformation mass spectrometry (FTMS) techniques to identify unique glycan markers in ovarian cancer cell lines which may be biomarkers for diagnosis of ovarian cancer. Glycan markers and CA125 levels are compared in a series of ovarian cancer patients and normal control subjects. Oligosaccharides (OS) were cleaved from the serum glycoproteins and isolated using solid phase extraction. MALDI-FTMS was then used to identify unique mass spectrometry (MS) peaks. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were calculated to measure the test performance of glycan markers. Sixteen unique OS MS signals were identified in ovarian cancer patient sera. Their additive mass/charge intensities were used to determine their presence or absence. The ovarian cancer patients varied in their disease status, with initial cancer stages ranging from IC to IV. Forty-four of 48 patients had detectable OS signals, with CA125 values between 2 and 17,044. Four patients had undetectable signals and their CA125 ranged between 7 and 10. Twenty-three of 24 control subjects had no detectable glycan markers, with CA125 levels between 10 and 64. Sensitivity and specificity values were determined to be 91.6% and 95.8%, respectively. The area under the ROC curve for all 72 samples was 0.954 (95% CI: 0.896, 1.0) using the glycomics assay, which was superior to CA125 in discriminating between cases and controls. This preliminary study suggests that glycomics profiling may be useful for the detection of ovarian cancer.

摘要

我们最近报道了使用基质辅助激光解吸电离(MALDI)傅里叶变换质谱(FTMS)技术来鉴定卵巢癌细胞系中的独特聚糖标志物,这些标志物可能是卵巢癌诊断的生物标志物。在一系列卵巢癌患者和正常对照受试者中比较了聚糖标志物和CA125水平。从血清糖蛋白中裂解出寡糖(OS),并使用固相萃取进行分离。然后使用MALDI-FTMS鉴定独特的质谱(MS)峰。计算敏感性、特异性和受试者操作特征(ROC)曲线下面积,以衡量聚糖标志物的检测性能。在卵巢癌患者血清中鉴定出16个独特的OS MS信号。它们的加和质荷比强度用于确定其存在与否。卵巢癌患者的疾病状态各不相同,初始癌症阶段从IC到IV。48例患者中有44例可检测到OS信号,CA125值在2至17,044之间。4例患者未检测到信号,其CA125在7至10之间。24例对照受试者中有23例未检测到聚糖标志物,CA125水平在10至64之间。敏感性和特异性值分别确定为91.6%和95.8%。使用糖组学分析,所有72个样本的ROC曲线下面积为0.954(95%CI:0.896,1.0),在区分病例和对照方面优于CA125。这项初步研究表明,糖组学分析可能有助于卵巢癌的检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e1c/2581843/3df5eb844790/nihms77352f1.jpg

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