Development of a nanoLC LTQ orbitrap mass spectrometric method for profiling glycans derived from plasma from healthy, benign tumor control, and epithelial ovarian cancer patients.

Development of a nanoLC LTQ orbitrap mass spectrometric method for profiling glycans derived from plasma from healthy, benign tumor control, and epithelial ovarian cancer patients.
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DOI:
10.1021/ac802262w
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发表时间:
2009-02-01
影响因子:
7.4
通讯作者:
Muddiman, David C.
Muddiman, David C.
中科院分区:
化学1区
文献类型:
--
作者:
Bereman, Michael S.;Williams, Taufika Islam;Muddiman, David C.

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We report the development of split-less nano-flow liquid chromatography mass spectrometric analysis of glycans chemically cleaved from glycoproteins in plasma. Porous graphitized carbon operating under reverse-phase conditions and an amide-based stationary phase operating under hydrophilic interaction conditions are quantitatively compared for glycan separation. Both stationary phases demonstrated similar column efficiencies and excellent retention time reproducibility without an internal standard to correct for retention time shift. The 95% confidence intervals of the mean retention times were ±4 seconds across 5 days of analysis for both stationary phases; however, the amide stationary phase was observed to be more robust. The high mass measurement accuracy of less than 2 ppm and fragmentation spectra provided highly confident identifications along with structural information. In addition, data are compared amongst samples derived from 10 healthy controls, 10 controls with a differential diagnosis of benign gynecologic tumors, and 10 diseased epithelial ovarian cancer patients (EOC). Two fucosylated glycans were found to be up-regulated in healthy controls and provided an accurate diagnostic value with an area under the receiver operator characteristic curve of 0.87. However, these same glycans provided a significantly less diagnostic value when used to differentiate EOC from benign tumor control samples with an area under the curve of 0.73.
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