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

Abstract

Ovarian cancer is often referred to as the “silent killer†due to the deadly nature of this malignancy and its asymptomatic nature. The disease will affect an estimated 24,000 women in the United States in 2009. If the disease is caught 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 early diagnosis are critical for both early intervention as well as a more in-depth understanding of this cancer such that therapeutic targets can be elucidated. One of the major limitations for biomarker discovery research is the massive amount of time that must be allocated for preparation and analysis of large sample sets. The recent development of hybrid ionization techniques which combine ambient analysis with limited sample preparation and lead to higher sample throughput could help circumvent this current limitation. Herein, the development of a newly introduced ionization technique termed desorption electrospray ionization (DESI) is characterized for various biomarker discovery applications 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 method is then utilized to compare the N-linked glycan profile between 48 plasma samples derived from epithelial ovarian cancer patients, 48 controls samples and 8 healthy samples. Three glycans were evaluated for their ability to differentiate between EOC and control and these results were compared to the gold standard in EOC detection, CA 125. Results indicated limited diagnostic value for three glycans in distinguishing control and EOC patients and moderate diagnostic value in differentiating EOC and healthy samples.