Serum paraoxonase 1 heteroplasmon, a fucosylated, and sialylated glycoprotein in distinguishing early hepatocellular carcinoma from liver cirrhosis patients

Aberrant glycan structure of serum glycoproteins creates unique patterns in different stages of hepatocellular carcinoma (HCC), which provides potential glycan biomarkers for early diagnosis of HCC. In this study, tandem lectin affinity chromatography using aleuria aurantia lectin (AAL) and wheat germ agglutinin (WGA) was processed to purify both fucosylated and sialylated serum glycoproteins from 27 liver cirrhosis (LC) and 27 early HCC patients, in which 122 glycoproteins were finally screened out by liquid chromatography-tandem mass spectrometry (LC-MSMS). Among the 122 proteins identified by LC-MSMS, 8 of them were only identified in HCC serum and another 6 existed only in LC serum. Serum paraoxonase 1 (PON1) was immunoprecipitated from 47 individual patients and blotted by lectins, showing enhanced fucosylation and sialylation in HCC serum than those in LC serum. The area under the ROC curve (AUROC) for AAL-reactive PON1 was 0.892 with a sensitivity of 71.4 and a specificity of 94.7 in differentiating early HCC from LC. Similarly, WGA-reactive PON1 had an AUROC of 0.902 with a sensitivity of 95.2 and a specificity of 78.9. The data indicated that the glycan differences of serum PON1 might serve as potential glycan biomarkers for distinguishing early HCC from LC patients.