Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics

Clinical Proteomics

Ramila Philip¹  Zacharie Nickens¹  Punit Shah¹  Julie Hafner¹  Vivekananda Shetty¹ 

[1] Immunotope, Inc., 3805 Old Easton Road, Doylestown, PA, 18902, USA

关键词: Western blot;    Mass spectrometry;    N-linked glycopeptides;    Lectin;    Sialylation;    Quantitative proteomics;    Ovarian cancer;   

Others  :  1026354
DOI  :  10.1186/1559-0275-9-10

 received in 2012-02-28, accepted in 2012-06-26,  发布年份 2012

【 摘 要 】

Background

In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. CA125 is currently used as the marker for ovarian cancer; however, it lacks specificity and sensitivity for detecting early stage disease. There is a critical unmet need for sensitive and specific routine screening tests for early diagnosis that can reduce ovarian cancer lethality by reliably detecting the disease at its earliest and treatable stages.

Results

In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/−) treatment confirmed the sialylation changes in the ovarian cancer samples.

Conclusion

Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer.

【 授权许可】

   
2012 Shetty et al.; licensee BioMed Central Ltd.

【 图 表 】

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