Protein glycosylation is one of the most significant post-translation modifications and plays a critical role in various biological functions. Haptoglobin (Hp) is one of the acute-phase response proteins secreted by liver. Its glycosylation could be analyzed by many analytical techniques qualitatively and quantitatively. The glycosylation alterations of Hp are reported to be associated with different kinds of diseases. The main glycosylation alterations of Hp in cancer appear to be the presence of aberrantly fucosylated and sialylated structures as well as increased branching. In this mini review, we provided a brief overview of Hp structure and biological function, discussed its glycosylation alterations in different cancers, and described the existing technologies for analyzing glycosylation site and glycan of Hp. Given the importance of Hp glycosylation, its unknown and unclear biological complexity and significances, Hp glycosylation has become a major target in cancer research. Development of sensitive and specific detection of Hp glycosylation including large-scale validation may be significant steps forward to its clinical application.
Aberrant fucosylation plays a functional role in regulating ontogeny and celluar differentiation and are differentially regulated in cancerous condition, which could provide hallmarks for cancer diagnostics and surveillance. We previously developed a magnetic beads-based lectin ELISA system to measure fucosylated haptoglobin (Hp), which has been reported to be a cancer biomarker through a series of glycoproteomic analysis. In this study, serum fucosylated Hp ratios were measured using our ELISA kit in a separate cohort of 260 patients independently, including 130 healthy controls and 130 patients with hepatocellular carcinoma (HCC). Fucosylated Hp /Hp ratio (levels of fucosylated Hp /levels of protein Hp) and ELISA Index (OD value of fucosylated Hp /OD value of protein Hp) were calculated respectively to reflect Hp fucosylation level on its protein level. Our data showed that fucosylated Hp /Hp ratio (AUC=0.8449) and ELISA Index (AUC=0.8581) had better performance in distinguishing HCC from controls, which indicated that fucosylated Hp ratios could improve the diagnosis and prediction of HCC even with a low level of alpha-fetoprotein (AFP). Additionally, the combination analysis of AFP and fucosylated Hp ratios increased the AUC value for HCC diagnosis.
Golgi protein 73 (GP73), a resident Golgi type-II membrane protein, is often upregulated in hepatocytes. In the present study, shRNA-mediated suppression of GP73 expression in hepatocellular carcinoma (HCC) cell lines (MHCC97H, HCCLM3) resulted in a significant inhibition of cell motility and invasion and also led to the regression of epithelial-mesenchymal transition phenotypes. In contrast, overexpression of GP73 in the SMMC7721 cell line retrieved the expression of EMT markers, and promoted cell motility and invasion. High expression of GP73 was also found in HCC tissues with metastasis, as detected by western blot and immunohistochemistry analyses. Kaplan-Meier survival analysis showed that the survival of patients with high GP73 expression was significantly poorer than that of patients with low GP73 expression (p=0.027). Our findings demonstrated an important role of GP73 in HCC metastasis, and indicated that GP73 is a candidate target for HCC therapy.
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