Identification of antibody against wingless‑type MMTV integration site family member 7B as a biliary cancer tumor marker

Takahashi,Mizuna; Takahashi,Mizuna; Tsuchikawa,Takahiro; Tsuchikawa,Takahiro; Hiwasa,Takaki; Hiwasa,Takaki; Nakamura,Toru; Nakamura,Toru; Hontani,Koji; Hontani,Koji; Kushibiki,Toshihiro; Kushibiki,Toshihiro; Inoko,Kazuho; Inoko,Kazuho; Takano,Hironobu; Takano,Hironobu; Hatanaka,Yutaka; Hatanaka,Yutaka; Matsushita,Kazuyuki; Matsushita,Kazuyuki; Matsubara,Hisahiro; Matsubara,Hisahiro; Hoshino,Tyuji; Hoshino,Tyuji; Ohtsuka,Masayuki; Ohtsuka,Masayuki; Shimada,Hideaki; Shimada,Hideaki; Tanaka,Kimitaka; Tanaka,Kimitaka; Nakanishi,Yoshitsugu; Nakanishi,Yoshitsugu; Asano,Toshimichi; Asano,Toshimichi; Noji,Takehiro; Noji,Takehiro; Okamura,Keisuke; Okamura,Keisuke; Shichinohe,Toshiaki; Shichinohe,Toshiaki; Hirano,Satoshi; Hirano,Satoshi

doi:10.3892/or.2022.8471

Identification of antibody against wingless‑type MMTV integration site family member 7B as a biliary cancer tumor marker

Authors:
- Mizuna Takahashi
- Takahiro Tsuchikawa
- Takaki Hiwasa
- Toru Nakamura
- Koji Hontani
- Toshihiro Kushibiki
- Kazuho Inoko
- Hironobu Takano
- Yutaka Hatanaka
- Kazuyuki Matsushita
- Hisahiro Matsubara
- Tyuji Hoshino
- Masayuki Ohtsuka
- Hideaki Shimada
- Kimitaka Tanaka
- Yoshitsugu Nakanishi
- Toshimichi Asano
- Takehiro Noji
- Keisuke Okamura
- Toshiaki Shichinohe
- Satoshi Hirano
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Affiliations: Department of Gastroenterological Surgery II, Faculty of Medicine, Hokkaido University, Sapporo 060‑8638, Japan, Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260‑8670, Japan, Research Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo 060‑8638, Japan, Department of Laboratory Medicine and Division of Clinical Genetics, Chiba University Hospital, Chiba 260‑8677, Japan, Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260‑8670, Japan, Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260‑8670, Japan, Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba 260‑8607, Japan, Department of Gastroenterological Surgery and Clinical Oncology, Toho University Graduate School of Medicine, Tokyo 143‑8541, Japan
Published online on: December 22, 2022 https://doi.org/10.3892/or.2022.8471
Article Number: 34

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Abstract

Biliary cancer has a poor prognosis due to a lack of specific biomarkers and difficulty in diagnosis. The present study aimed to identify serum tumor markers for the diagnosis of biliary cancer via serological identification of antigens by recombinant cDNA expression cloning. Wingless‑type MMTV integration site family, member 7 (WNT7B) was identified as a target antigen, suggesting the presence of serum antibodies against this antigen. Deletion mutants were then prepared to evaluate the response to serum antibodies. When serum antibody levels against WNT7B deletion mutants (WNT7B_-92‑2, _-92‑260, _2-260 and _184-260) were examined using amplified luminescence proximity homogeneous assay‑linked immunosorbent assay, the levels of the antibody against WNT7B with amino acids 184‑260 were higher in patients with biliary cancer than in healthy donors. Therefore, the region covering residues 184‑260 of WNT7B was decomposed to generate seven peptides, and the levels of antibodies against these peptides were measured. Among them, the levels of antibodies against WNT7B_234‑253 and WNT7B_244‑260 were higher in patients with biliary cancers than in healthy donors (WNT7B_234‑253, P=0.0009; WNT7B_244‑260, P=0.0005). The levels of the antibody against the former were specifically high in patients with biliary cancer but not in those with esophageal, gastric, colorectal, pancreatic, or breast cancer. Furthermore, analysis by the cutoff value of WNT7B_234‑253 defined by ROC showed a high sensitivity of 70% in patients with biliary cancer. Therefore, the serum levels of the antibody against WNT7B_234‑253 may be useful as a marker for biliary cancer diagnosis.

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