Skip to main content

Advertisement

Log in

Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sanyal, A.J., Yoon, S.K., Lencioni, R.: The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist 15, 14–22 (2010)

    Article  PubMed  Google Scholar 

  2. Liu, J., Fan, D.: Hepatitis B in China. Lancet 369, 1582–1583 (2007)

    Article  PubMed  Google Scholar 

  3. Hart, G.W., Copeland, J.: Glycomics hits the big time. Cell 143, 672–676 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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)

    PubMed  PubMed Central  Google Scholar 

  5. 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)

    Article  CAS  PubMed  Google Scholar 

  6. 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)

    Article  CAS  PubMed  Google Scholar 

  7. 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)

    Article  CAS  PubMed  Google Scholar 

  8. 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)

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Google Scholar 

  10. 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)

    CAS  PubMed  Google Scholar 

  11. 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)

    Article  CAS  PubMed  Google Scholar 

  12. 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)

    Article  CAS  PubMed  Google Scholar 

  13. 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)

    Article  CAS  Google Scholar 

  14. 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)

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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)

    Article  CAS  PubMed  Google Scholar 

  16. Blomme, B., Van Steenkiste, C., Callewaert, N., Van Vlierberghe, H.: Alteration of protein glycosylation in liver diseases. J. Hepatol 50, 592–603 (2009)

    Article  CAS  PubMed  Google Scholar 

  17. 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)

  18. Hirabayashi, J., Kuno, A., Tateno, H.: Development and applications of the lectin microarray. Top. Curr. Chem. 367, 105–124 (2015)

    Article  PubMed  Google Scholar 

  19. 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)

    Article  CAS  PubMed  Google Scholar 

  20. 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)

    Article  CAS  PubMed  Google Scholar 

  21. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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)

    Article  CAS  PubMed  Google Scholar 

  23. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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)

    Article  CAS  PubMed  Google Scholar 

  25. 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)

    PubMed  Google Scholar 

  26. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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)

    Article  CAS  PubMed  Google Scholar 

  28. Ma, B., Simala-Grant, J.L., Taylor, D.E.: Fucosylation in prokaryotes and eukaryotes. Glycobiology 16, 158R–184R (2006)

    Article  CAS  PubMed  Google Scholar 

  29. 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)

    Article  PubMed  Google Scholar 

  30. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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)

    PubMed  PubMed Central  Google Scholar 

  32. Ramachandran, P., Iredale, J.P., Fallowfield, J.A.: Resolution of liver fibrosis: basic mechanisms and clinical relevance. Semin. Liver Dis. 35, 119–131 (2015)

    Article  CAS  PubMed  Google Scholar 

  33. 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)

    Article  CAS  PubMed  Google Scholar 

  34. 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)

    Article  CAS  PubMed  Google Scholar 

  35. 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)

    Article  PubMed  Google Scholar 

  36. 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)

    Article  Google Scholar 

Download references

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

Authors

Corresponding authors

Correspondence to Chen Huang or Zheng Li.

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)

High Resolution image (TIF 5131 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-015-9645-z

Keywords

Navigation