In order to discover potential glycoprotein biomarkers in ovarian cancer, we applied a lectin array and Exactag labeling based quantitative glycoproteomics approach. A lectin array strategy was used to detect overall lectin-specific glycosylation changes in serum proteins from patients with ovarian cancer and those with benign conditions. Lectins, which showed significant differential response for fucosylation, were used to extract glycoproteins that had been labeled using isobaric chemical tags. The glycoproteins were then identified and quantified by LC-MS/MS, and five glycoproteins were found to be differentially expressed in the serum of ovarian cancer patients compared to benign diseases. The differentially expressed glycoproteins were further confirmed by lectin-ELISA and ELISA assay. Corticosteroid-binding globulin (CBG), serum amyloid p component (SAP), complement factor B (CFAB), and histidine-rich glycoprotein (HRG) were identified as potential markers for differentiating ovarian cancer from benign diseases or healthy controls. A combination of CBG and HRG (AUC = 0.825) showed comparable performance to CA125 (AUC = 0.829) in differentiating early stage ovarian cancer from healthy controls. The combination of CBG, SAP, and CA125 showed improved performance for distinguishing stage III ovarian cancer from benign diseases compared to CA125 alone. The ability of CBG, SAP, HRG, and CFAB to differentiate the serum of ovarian cancer patients from that of controls was tested using an independent set of samples. Our findings suggest that glycoprotein modifications may be a means to identify novel diagnostic markers for detection of ovarian cancer.
"Lectins are carbohydrate-binding proteins that contain at least one non-catalytic domain that binds reversibly with mono- or oligosaccharides with high specificity (4). Therefore, lectins may be useful tools for analyzing glycofiles and may be used as biomarkers for a variety of types of cancer, including aggressive breast (5,6), ovarian (7), pancreatic (8), prostate (9) and liver (10) cancer. The monocot mannose-binding lectin, Pinellia pedatisecta agglutinin (PPA), accumulates in the tuber of P. pedatisecta, a species of the Araceae family. "
[Show abstract][Hide abstract] ABSTRACT: The analysis of altered glycosylation patterns may provide biomarkers for various types of cancer. The present study developed a Pinellia pedatisecta agglutinin (PPA)-based lectin blot analysis technique, which was used to analyze the glycosylation patterns in various types of cancer cells. Results showed that a typical band located between 47 and 85 kDa was obtained in the HL60 leukemia cells, whereas three typical bands located between 20 and 47 kDa were observed in the Kasumi-1 leukemia cells. For the PLC, BEL-7404, Huh7 and H1299 solid tumor cell lines, different band patterns were detected, with bands typically located between 55 and 100 kDa. The findings of the present study show that PPA-based lectin blot analysis is capable of distinguishing between glycosylation patterns in leukemia and solid tumor cell lines. The glycofiles detected using PPA-based lectin blot analysis may provide a 'glycosylation fingerprint' for a variety of cancer cells, which may be valuable for cancer prognosis and diagnosis.
"With the further confirmation by lectin-ELISA and ELISA assay, corticosteroid-binding globulin (CBG) and other four glycosylated-proteins were identified as potential markers for differentiating ovarian cancer from benign diseases or healthy controls. Especially, the combination of CBG, SAP, and CA125 showed improved performance for distinguishing stage III ovarian cancer from benign diseases compared to CA125 alone . These above findings clearly suggest that glycosylated-protein modifications may be a useful means to identify novel markers for detection of cancer and monitoring of cancer progression. "
[Show abstract][Hide abstract] ABSTRACT: Glycosylation is estimated to be found in over 50% of human proteins. Aberrant protein glycosylation and alteration of glycans are closely related to many diseases. More than half of the cancer biomarkers are glycosylated-proteins, and specific glycoforms of glycosylated-proteins may serve as biomarkers for either the early detection of disease or the evaluation of therapeutic efficacy for treatment of diseases. Glycoproteomics, therefore, becomes an emerging field that can make unique contributions to the discovery of biomarkers of cancers. The recent advances in mass spectrometry (MS)-based glycoproteomics, which can analyze thousands of glycosylated-proteins in a single experiment, have shown great promise for this purpose. Herein, we described the MS-based strategies that are available for glycoproteomics, and discussed the sensitivity and high throughput in both qualitative and quantitative manners. The discovery of glycosylated-proteins as biomarkers in some representative diseases by employing glycoproteomics was also summarized.
"Wu et al. used lectin array method to identify and confirm differentially expressed fucosylated glycoproteins in serum of patients with different stage ovarian cancer . Fucosylated glycoproteins extracted using LCA and UEAI lectins were labeled with isobaric chemical tags labeling. "
[Show abstract][Hide abstract] ABSTRACT: Glycosylation is one of the most important posttranslational modifications of proteins and plays essential roles in various biological processes. Aberration in the glycan moieties of glycoproteins is associated with many diseases. It is especially critical to develop the rapid and sensitive methods for analysis of aberrant glycoproteins associated with diseases. Mass spectrometry (MS) has become a powerful tool for glycoprotein analysis. Especially, tandem mass spectrometry can provide highly informative fragments for structural identification of glycoproteins. This review provides an overview of the development of MS technologies and their applications in identification of abnormal glycoproteins and glycans in human serum to screen cancer biomarkers in recent years.
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