Prohaptoglobin is a possible prognostic biomarker for colorectal cancer

Koichi Morishita; Jumpei Kondo; Daisuke Sakon; Ayumu Hayashibara; Ikumi Tamura; Kayoko Shimizu; Shinji Takamatsu; Kohei Murata; Yoshihiro Kamada; Eiji Miyoshi

doi:10.1016/j.bbrc.2023.06.017

Prohaptoglobin is a possible prognostic biomarker for colorectal cancer

Biochem Biophys Res Commun. 2023 Sep 10:672:72-80. doi: 10.1016/j.bbrc.2023.06.017. Epub 2023 Jun 9.

Authors

Affiliations

¹ Department of Molecular Biochemistry and Clinical Investigation Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
² Medical Systems Research & Development Center, Medical Systems Business Div. FUJIFILM Corporation, Amagasaki, Hyogo, Japan.
³ Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan.
⁴ Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
⁵ Department of Molecular Biochemistry and Clinical Investigation Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: emiyoshi@sahs.med.osaka-u.ac.jp.

PMID: 37343317
DOI: 10.1016/j.bbrc.2023.06.017

Abstract

Background and aims: Fucosylated haptoglobin is a novel glycan biomarker for colorectal and other cancers, while the significance of its precursor, prohaptoglobin (proHp), remains to be elucidated. In this study, we investigated whether proHp can be a colorectal cancer (CRC) biomarker and the biological functions of proHp in CRC using 10-7G, a monoclonal antibody recently developed in our laboratory.

Materials and methods: Serum proHp level in 74 patients with CRC was semi-quantified by western blotting, and 5-year recurrence-free survival and overall survival were analyzed for groups stratified by proHp status (high vs. low). We also performed immunohistochemical analyses of 17 CRC tissue sections using 10-7G mAb. The biological functions of proHp were evaluated by overexpressing proHp in CRC cell lines.

Results: Serum proHp correlated with the clinical stage and poorer prognosis of CRC. In the primary CRC sections, immune cells were stained positive for 10-7G in ∼50% of the cases. Overexpression of proHp in HCT116 human CRC cells induced epithelial-mesenchymal transition-like changes and promoted cell migration in CRC cells.

Conclusion: We provide evidence for the first time that proHp has potential as a prognostic biomarker for CRC and demonstrated specific biological activities of proHp.

Keywords: Colorectal cancer; EMT; Migration; Pro-haptoglobin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Cell Proliferation
Colorectal Neoplasms* / metabolism
Epithelial-Mesenchymal Transition
HCT116 Cells
Haptoglobins* / metabolism
Humans
Prognosis

Substances

prohaptoglobin
Haptoglobins