Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Development of cancer biomarker for biliary tract cancer and pancreatic cancer with serum haptoglobin glycan analyses (#136)

Miyako Nakano 1 , Soya Usui 1 , Taiki Sugiyama 1 , Shiro Takahashi 1 , Eiji Miyoshi 2
  1. Unit of Biotechnology, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima, JP
  2. Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, JP

[Background] Biliary tract and pancreas are located in the deep part of the body. Therefore, it is difficult to find out genesis of cancer and is associated with poor prognosis. Biliary tract is pathway of bile, composed of bile ducts and gall bladder. We previously reported that fucosylated glycans of serum haptoglobin (Hpt) were significantly increased in serum samples of pancreatic cancer. In this study, we investigated whether this serum fucosylated Hpt is a cancer biomarker that can distinguish between bile duct cancer and gall bladder cancer and whether or not the increase of fucosylated glycans also occurred on cell membrane proteins in pancreatic cancer tissue.

[Methods] Hpt derived from serum of patients with biliary tract cancers was immunoprecipitated and subjected to SDS-PAGE and then transferred onto PVDF membrane. Cell membrane proteins derived from tumor section and their surrounding non-tumor section of pancreatic tissue was dotted onto PVDF membrane. N-Glycans were released from Hpt or cell membrane proteins by PNGaseF, and structural glycan analyses were performed by LC-ESI MS.

[Results] Lewis-fucosylated glycans on Hpt were significantly increased in samples of both gall bladder cancer and bile duct cancer. Core-fucosylated glycans on Hpt were significantly increased in sample of only bile duct cancer. N-Glycans containing ABO antigens were significantly decreased in tumor sections of pancreatic tissue, whereas they were observed as major components in tumor sections.

[Conclusion] We speculate that increases in Lewis-fucosylated Hpt are due to binding with hemoglobin in the bloodstream which is increased by genesis of cancer. Increases in core-fucosylated Hpt are due to choking of cancer cells in the bile duct, and bile flowing normally into duodenum flows back into bloodstream. We suggest the reduced activity of fucosyltransferase involving synthesis of H antigen results in decrease of ABO antigens in tumor section.

[Keywords] haptoglobin, cancer-biomarker