N-glycans for the detection of hepatocellular carcinoma:

Investigators:

Radoslav Goldman, PhD

Hypotheses/Aims

This study will evaluate changes in protein associated N-glycans in HCC. The investigators identified 3 N-glycans as candidate markers using MALDI-TOF mass spectrometric quantification of permethylated N-glycan structures, enzymatically released from serum glycoproteins. They tested this method in a pilot set of HCC cases and controls from a study in Egypt. The study population included 73 HCC cases [49 HCV RNA+] [18 early stage, 33 advanced, others not staged], 77 controls with no liver disease, and 52 controls with CLD and no HCC [all HCV RNA+] (22 fibrosis, 25 cirrhosis, 5 not staged). Initial analysis was performed on a randomly selected training set. Individual N-glycans and a combined support vector machine were used to classify blinded spectra from validation samples. AUROC for individual glycans was 89-93%, while the 3 glycans combined detected HCC with 90% sensitivity and 89% specificity. 17 of 18 early stage HCC and 23 of 25 cirrhosis controls were correctly classified by this method. In this same study, 30% of HCC cases had AFP <200 ng/mL, and 18 of these 22 cases were correctly classified by the N-glycans, indicating the two tests are complementary.  The investigators expect that the quantification of glycans will improve the performance of currently available methods for the early detection of HCC.