A lectin-coupled, targeted proteomic mass spectrometry (MRM MS) platform for identification of multiple liver cancer biomarkers in human plasma

• Published in: Journal of proteomics 2012-09, Vol.75 (17), p.5507-5515
• Main Authors: Ahn, Yeong Hee, Shin, Park Min, Oh, Na Ree, Park, Gun Wook, Kim, Hoguen, Yoo, Jong Shin
• Format: Article
• Language: English
• Subjects: Aberrant glycosylation; antibodies; Biological and medical sciences; biomarkers; Diverse techniques; fractionation; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; glycoproteins; glycosylation; Hepatitis B virus; hepatoma; humans; immunoassays; Lectin; lectins; Liver cancer biomarker; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Mass spectrometry; Medical sciences; Molecular and cellular biology; monitoring; Multiple reaction monitoring; proteomics; quantitative analysis; Tumors
• ISSN: 1874-3919
• DOI: 10.1016/j.jprot.2012.06.027

Aberrantly glycosylated proteins related to liver cancer progression were captured with specific lectin and identified from human plasma by multiple reaction monitoring (MRM) mass spectrometry as multiple biomarkers for hepatocellular carcinoma (HCC). The lectin fractionation for fucosylated protein glycoforms in human plasma was conducted with a fucose-specific aleuria aurantia lectin (AAL). Following tryptic digestion of the lectin-captured fraction, plasma samples from 30 control cases (including 10 healthy, 10 hepatitis B virus [HBV], and 10 cirrhosis cases) and 10 HCC cases were quantitatively analyzed by MRM to identify which glycoproteins are viable HCC biomarkers. A1AG1, AACT, A1AT, and CERU were found to be potent biomarkers to differentiate HCC plasma from control plasmas. The AUROC generated independently from these four biomarker candidates ranged from 0.73 to 0.92. However, the lectin-coupled MRM assay with multiple combinations of biomarker candidates is superior statistically to those generated from the individual candidates with AUROC more than 0.95, which can be an alternative to the immunoassay inevitably requiring tedious development of multiple antibodies against biomarker candidates to be verified. Eventually the lectin-coupled, targeted proteomic mass spectrometry (MRM MS) platform was found to be efficient to identify multiple biomarkers from human plasma according to cancer progression. [Display omitted] ► Lectin-coupled MRM-based identification of liver cancer biomarkers. ► A1AG1, AACT, A1AT, and CERU can be HCC biomarkers. ► Lectin-specific biomarker based on aberrant protein glycosylation