The Development of Desorption Electrospray Ionization and Nano Flow Liquid Chromatography Mass Spectrometric Methods for Glycan Analysis: Applications for Biomarker Discovery in Epiethelial Ovarian Cancer

FT-ICR;Glycan Profiling;Glycosylation;Ovarian Cancer;Mass Spectrometry

Bereman, Michael Seth ; David Muddiman, Committee Chair,Lin He, Committee Member,Chris Gorman, Committee Member,Edmond Bowden, Committee Member,Bereman, Michael Seth ; David Muddiman ; Committee Chair ; Lin He ; Committee Member ; Chris Gorman ; Committee Member ; Edmond Bowden ; Committee Member

University:North Carolina State University

关键词: FT-ICR;    Glycan Profiling;    Glycosylation;    Ovarian Cancer;    Mass Spectrometry;   

Others  :  https://repository.lib.ncsu.edu/bitstream/handle/1840.16/4709/etd.pdf?sequence=1&isAllowed=y

美国|英语

来源: null

【 摘 要 】

Ovarian cancer is often referred to as the “silent killerâ€Âdue to the deadlynature of this malignancy and its asymptomatic nature. The disease will affectan estimated 24,000 women in the United States in 2009. If the disease iscaught in its early stages over 90 % of patients survive longer than 5 years;however, 7 out of 10 patients are diagnosed in the late stages, after metastasis,where 1 in 5 people meet this 5-year survival mark. Advancements in earlydiagnosis are critical for both early intervention as well as a more in-depthunderstanding of this cancer such that therapeutic targets can be elucidated.One of the major limitations for biomarker discovery research is themassive amount of time that must be allocated for preparation and analysis oflarge sample sets. The recent development of hybrid ionization techniqueswhich combine ambient analysis with limited sample preparation and lead tohigher sample throughput could help circumvent this current limitation. Herein,the development of a newly introduced ionization technique termed desorptionelectrospray ionization (DESI) is characterized for various biomarker discoveryapplications including proteomics and glycomics.Glycomics is an emerging field for biomarker discovery research.Herein, a method for the analysis of N-linked glycans is provided. This methodis then utilized to compare the N-linked glycan profile between 48 plasmasamples derived from epithelial ovarian cancer patients, 48 controls samplesand 8 healthy samples. Three glycans were evaluated for their ability todifferentiate between EOC and control and these results were compared to thegold standard in EOC detection, CA 125. Results indicated limited diagnosticvalue for three glycans in distinguishing control and EOC patients and moderatediagnostic value in differentiating EOC and healthy samples.