Abstract
The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies.
Similar content being viewed by others
References
Sanyal, A.J., Yoon, S.K., Lencioni, R.: The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist 15, 14–22 (2010)
Liu, J., Fan, D.: Hepatitis B in China. Lancet 369, 1582–1583 (2007)
Hart, G.W., Copeland, J.: Glycomics hits the big time. Cell 143, 672–676 (2010)
Malaguarnera, G., Bertino, G., Vacante, M., Malaguarnera, M.: Hepatocellular carcinoma markers in the omics era: the glycomic analysis. Hepatobiliary Surg. Nutr. 3, 407–409 (2014)
Kamiyama, T., Yokoo, H., Furukawa, J., Kurogochi, M., Togashi, T., Miura, N., et al.: Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis. Hepatology 57, 2314–2325 (2013)
Mann, A.C., Record, C.O., Self, C.H., Turner, G.A.: Monosaccharide composition of haptoglobin in liver-diseases and alcohol-abuse – large changes in glycosylation associated with alcoholic liverdisease. Clin. Chim. Acta 227, 69–78 (1994)
Chambers, W., Thompson, S., Skillen, A.W., Record, C.O., Turner, G.A.: Abnormally fucosylated haptoglobin as a marker for alcoholic liver-disease but not excessive alcohol-consumption or Nonalcoholic liver-disease. Clin. Chim. Acta 219, 177–182 (1993)
Nakagawa, T., Uozumi, N., Nakano, M., Mizuno-Horikawa, Y., Okuyama, N., Taguchi, T., et al.: Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts. J. Biol. Chem. 281, 29797–29806 (2006)
Miyahara, K., Nouso, K., Dohi, C., Morimoto, Y., Kinugasa, H., Wada, N., et al.: Alteration of N-glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma. Hepatol. Res. (2014). doi:10.1111/hepr.12441
Yang, X.P., Tang, J., Rogler, C.E., Stanley, P.: Reduced hepatocyte proliferation is the basis of retarded liver tumor progression and liver regeneration in mice lacking N-acetylglucosaminyltransferase III. Cancer Res. 63, 7753–7759 (2003)
Yanagi, M., Aoyagi, Y., Suda, T., Mita, Y., Asakura, H.: Nacetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma. J. Gastroenterol. Hepatol. 16, 1282–1289 (2001)
Ohno, M., Nishikawa, A., Koketsu, M., Taga, H., Endo, Y., Hada, T., et al.: Enzymatic basis of sugar structures of alpha-fetoprotein in hepatoma and hepatoblastoma cell lines: correlation with activities of alpha 1–6 fucosyltransferase and N-acetylglucosaminyltransferases III and V. Int. J. Cancer 51, 315–317 (1992)
Li, J., Gao, J., Jiang, M., Chen, J., Liu, Z., Chen, P., et al.: Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity enrichment and mass spectrometric identification. Biochemistry (Mosc) 80, 260–275 (2015)
Sun, Z., Sun, D., Wang, F., Cheng, K., Zhang, Z., Xu, B., et al.: Differential analysis of N-glycoproteome between hepatocellular carcinoma and normal human liver tissues by combination of multiple protease digestion and solid phase based labeling. Clin. Proteomics 11, 26 (2014)
Zhu, J., Sun, Z., Cheng, K., Chen, R., Ye, M., Xu, B., et al.: Comprehensive mapping of protein N-glycosylation in human liver by combining hydrophilic interaction chromatography and hydrazide chemistry. J. Proteome Res. 13, 1713–1721 (2014)
Blomme, B., Van Steenkiste, C., Callewaert, N., Van Vlierberghe, H.: Alteration of protein glycosylation in liver diseases. J. Hepatol 50, 592–603 (2009)
Yamashita, K., Kuno, A., Matsuda, A., Ikehata, Y., Katada, N., Hirabayashi, J., et al.: Lectin microarray technology identifies specific lectins related to lymph node metastasis of advanced gastric cancer. Gastric. Cancer (2015)
Hirabayashi, J., Kuno, A., Tateno, H.: Development and applications of the lectin microarray. Top. Curr. Chem. 367, 105–124 (2015)
Qin, Y., Zhong, Y., Dang, L., Zhu, M., Yu, H., Chen, W., et al.: Alteration of protein glycosylation in human hepatic stellate cells activated with transforming growth factor-β1. J. Proteomics 75, 4114–4123 (2012)
Qin, Y., Zhong, Y., Zhu, M., Dang, L., Yu, H., Chen, Z., et al.: Age- and sex-associated differences in the glycopatterns of human salivary glycoproteins and their roles against influenza A virus. J. Proteome Res. 12, 2742–2754 (2013)
Zhong, Y., Qin, Y., Yu, H., Yu, J., Wu, H., Chen, L., et al.: Avian influenza virus infection risk in humans with chronic diseases. Sci. Rep. 5, 8971 (2015)
Yu, H., Zhu, M., Qin, Y., Zhong, Y., Yan, H., Wang, Q., et al.: Analysis of glycan-related genes expression and glycan profiles in mice with liver fibrosis. J. Proteome Res. 11, 5277–5285 (2012)
Nakajima, K., Inomata, M., Iha, H., Hiratsuka, T., Etoh, T., Shiraishi, N., et al.: Establishment of new predictive markers for distant recurrence of colorectal cancer using lectin microarray analysis. Cancer Med. 4, 293–302 (2015)
Yasuda, E., Sako, T., Tateno, H., Hirabayashi, J.: Application of lectin microarray to bacteria including lactobacillus casei/paracasei strains. Methods Mol. Biol. 1200, 295–311 (2014)
Ju, T., Aryal, R.P., Kudelka, M.R., Wang, Y., Cummings, R.D.: The cosmc connection to the Tn antigen in cancer. Cancer Biomark. 14, 63–81 (2014)
Haugstad, K.E., Gerken, T.A., Stokke, B.T., Dam, T.K., Brewer, C.F., Sletmoen, M.: Enhanced self-association of mucins possessing the T and Tn carbohydrate cancer antigens at the single-molecule level. Biomacromolecules 13, 1400–1409 (2012)
Yu, L.G., Milton, J.D., Fernig, D.G., Rhodes, J.M.: Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins. J. Cell. Physiol. 186, 282–287 (2001)
Ma, B., Simala-Grant, J.L., Taylor, D.E.: Fucosylation in prokaryotes and eukaryotes. Glycobiology 16, 158R–184R (2006)
Olewicz-Gawlik, A., Korczowska-Łacka, I., Łacki, J.K., Klama, K., Hrycaj, P.: Fucosylation of serum alpha1-acid glycoprotein in rheumatoid arthritis patients treated with infliximab. Clin. Rheumatol. 26, 1679–1684 (2007)
Terao, N., Takamatsu, S., Minehira, T., Sobajima, T., Nakayama, K., Kamada, Y., et al.: Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like phenotypes. World J. Gastroenterol. 21, 3876–3887 (2015)
Desiderio, V., Papagerakis, P., Tirino, V., Zheng, L., Matossian, M., Prince, M.E., et al.: Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells. Oncotarget 6, 71–84 (2015)
Ramachandran, P., Iredale, J.P., Fallowfield, J.A.: Resolution of liver fibrosis: basic mechanisms and clinical relevance. Semin. Liver Dis. 35, 119–131 (2015)
Ji, J., Eggert, T., Budhu, A., Forgues, M., Takai, A., Dang, H., et al.: Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma. Hepatology 62, 481–495 (2015)
Hebert, D.N., Garman, S.C., Molinari, M.: The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol. 15, 364–370 (2005)
De Graffenried, C.L., Bertozzi, C.R.: The roles of enzyme localisation and complex formation in glycan assembly within the Golgi apparatus. Curr. Opin. Cell Biol. 16, 356–363 (2004)
Bekesovaa, S., Kostia, O., Chandlera, K.B., Wua, J., Madeja, H.L., Browna, K.C., et al.: N-glycans in liver-secreted and immunoglogulin-derived protein fractions. J. Proteomics 75, 2216–2224 (2012)
Acknowledgments
This work was supported by National Natural Science Foundation of China (81401137), the Fundamental Research Funds for the Central Universities, China (XJJ2014069), and China Postdoctoral Science Foundation (2015 M572574).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no competing financial interests.
Additional information
Yannan Qin and Yaogang Zhong contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(GIF 107 kb)
Rights and permissions
About this article
Cite this article
Qin, Y., Zhong, Y., Ma, T. et al. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV. Glycoconj J 33, 125–136 (2016). https://doi.org/10.1007/s10719-015-9645-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-015-9645-z