Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in protein associated glycans associated with the development of hepatocellular carcinoma. To achieve this goal, we developed mass spectrometric analysis of permethylated glycans enzymatically removed from serum proteins. This method allows an efficient and high-throughput comparison of glycans. We tested the method on a pilot set of hepatocellular carcinoma cases and controls from our unique study of hepatocellular carcinoma in Egypt, a country with an epidemic of hepatitis C viral infection. The pilot-study identified three glycans that predict hepatocellular carcinoma with 90% prediction accuracy compared to controls with chronic liver disease. In this study, we propose to expand the project and to include a comparison of hepatocellular carcinoma cases and chronic liver disease controls in the US population. As we continue to assess glycan changes in the progression of chronic viral infection to hepatocellular carcinoma, we will continue to improve the analytical methods for quantification and structural characterization of the glycans. It is expected that the quantification of glycans will improve the performance of currently available methods for early detection of hepatocellular carcinoma. Defining clinically applicable markers of early-stage cancer has potentially far-reaching consequences for disease management and patient health. The glycan markers could be used to screen high risk populations for early signs of disease;to design and test new chemoprevention strategies;and to follow disease progression after treatment. Identification of the changes in glycans associated with disease progression is expected to generate new hypotheses for carcinogenesis of the liver.
Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in various protein-decorating sugars that accompany the development of liver cancer. To achieve this goal, we developed methods that allow high-throughput comparison of these sugars. The identified sugars could be used to screen high risk populations for early signs of liver cancer;to design and test new chemoprevention strategies;and to follow disease progression after treatment.
|Kozlik, Petr; Goldman, Radoslav; Sanda, Miloslav (2018) Hydrophilic interaction liquid chromatography in the separation of glycopeptides and their isomers. Anal Bioanal Chem 410:5001-5008|
|Fan, Yu; Hu, Yu; Yan, Cheng et al. (2018) Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer. Sci Rep 8:4322|
|Sanda, Miloslav; Zhang, Lihua; Edwards, Nathan J et al. (2017) Site-specific analysis of changes in the glycosylation of proteins in liver cirrhosis using data-independent workflow with soft fragmentation. Anal Bioanal Chem 409:619-627|
|Kozlik, Petr; Sanda, Miloslav; Goldman, Radoslav (2017) Nano reversed phase versus nano hydrophilic interaction liquid chromatography on a chip in the analysis of hemopexin glycopeptides. J Chromatogr A 1519:152-155|
|Darebna, Petra; Novak, Petr; Kucera, Radek et al. (2017) Changes in the expression of N- and O-glycopeptides in patients with colorectal cancer and hepatocellular carcinoma quantified by full-MS scan FT-ICR and multiple reaction monitoring. J Proteomics 153:44-52|
|Kozlik, Petr; Goldman, Radoslav; Sanda, Miloslav (2017) Study of structure-dependent chromatographic behavior of glycopeptides using reversed phase nanoLC. Electrophoresis 38:2193-2199|
|Wang, Mengjun; Sanda, Miloslav; Comunale, Mary Ann et al. (2017) Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC. Cancer Epidemiol Biomarkers Prev 26:795-803|
|Flowers, Sarah A; Zhou, Xin; Wu, Jing et al. (2016) Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck. Oncotarget 7:43177-43187|
|Sanda, Miloslav; Benicky, Julius; Wu, Jing et al. (2016) Increased sialylation of site specific O-glycoforms of hemopexin in liver disease. Clin Proteomics 13:24|
|Sanda, Miloslav; Goldman, Radoslav (2016) Data Independent Analysis of IgG Glycoforms in Samples of Unfractionated Human Plasma. Anal Chem 88:10118-10125|
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