N‐glycan based models improve diagnostic efficacies in hepatitis B virus‐related hepatocellular carcinoma

Abstract

The early diagnosis of hepatocellular carcinoma (HCC) is of great clinical desirable due to lack of specific and sensitive markers. Alterations in the sugar chains of glycoprotein synthesized by the liver contribute to the molecular basis of abnormalities in carcinogenesis. This study aims to construct and assess the diagnostic value of N-glycan based diagnostic model in HCC identification and follow-up. A total of 393 subjects including HBV-related HCC, liver fibrosis and healthy controls were recruited. Follow-up was carried out before and after surgical treatment in HCC. N-glycome of serum glycoprotein was profiled by DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Multiparameters diagnostic models were constructed based on N-glycan markers. The result found that 2 N-glycan structure abundances (NG1A2F, Peak 4; NA3Fb, Peak 9) were useful as N-glycan markers. The diagnostic efficacy of the log ratio [log(p9/4)] was similar to that of AFP in differentiating HCC from fibrosis. The accuracy and sensitivity of the diagnostic model combining AFP and N-glycan markers (Cscore B) were increased 7-10% compared with that of AFP. Log(p9/4) was more efficient in monitoring the progression of HCC with regarding to vascular invasion at improved specificity (16%) and accuracy (8%) compared with that of AFP. The N-glycan markers were found to be changed significantly after surgical resection in HCC follow-up. We conclude that the branching a (1,3)-fucosylated triantennary glycan and a biantennary glycan are promising as N-glycan markers. The diagnostic models based on the N-glycan markers and AFP improve the efficacy in HCC diagnosis and progression monitoring.Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are frequent causes of acute and chronic hepatitis worldwide and leading causes for hepatic cirrhosis and cancer. There is a distinct geographical variation in HBV and HCV infection incidence and prevalence in different regions. Chronic HBV infection is a serious health threat in the Asian-Pacific region. Of the estimated 50 million new cases of HBV infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these are in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. 1

The diagnostic value of serum fucosylated fetuin A in hepatitis B virus-related liver diseases

“…It's worth noting that in our study the fuc-fetuin A concentration could not distinguish HCC from LC, which is not consistent with our previous reports in which the total specific fucosylated N-glycan in serum was used to differentiate HCC and LC [3,17]. We attributed this to the different type of main fucosylation for fetuin A in HCC and LC, because the AAL lectin used in the present study bind both core and out arm fucosylated glycan.…”

“…Many reports have revealed that increases in the levels of fucosylation of serum glycoproteins occur with the development of HCC [13][14][15][16]. Previous studies from our group also validated these variances between the sera of HBV-related HCC patients and fibrosis or cirrhosis patients in Chinese population [3,17]. As for fetuin A, it has also been reported that its concentration in serum decreased in both LC and HCC [11], while the fucosylated level of fetuin A elevated in HCC [5,16].…”

“…In addition, the difference of outer arm fucosylation between HCC and LC patients was significant [15], and experimental evidence revealed the up-regulation of the branched multiple fucosylated glycoforms in cancer disease [32]. Our group has also reported that increased outer arm fucosylation was observed in HCC patients, while core fucosylation was up-regulated in LC patients [3,17].…”

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

“…DSA-FACE is a simple and efficient technology for measuring N-glycan changes in serum. We previously used the technology to assist in the diagnosis of HCC, CRC, and gastric cancer [29][30][31]. The study was designed to target analysis of the aberrant N-glycans.…”

Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma

“…Total serum glycoproteins, serum IgG, IgG-L3, and IgG-L3 lacking core-fucose were analyzed for N-glycan structure with DSA-FACE as described previously. 33,34 The results were analyzed using the GeneMapper v3.7 software (Life Technologies Corporation).…”