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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Cytokines | Research

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis

Authors: Mitsuru Sugimoto, Rei Suzuki, Yoshihiro Nozawa, Tadayuki Takagi, Naoki Konno, Hiroyuki Asama, Yuki Sato, Hiroki Irie, Jun Nakamura, Mika Takasumi, Minami Hashimoto, Tsunetaka Kato, Ryoichiro Kobashi, Osamu Suzuki, Yuko Hashimoto, Takuto Hikichi, Hiromasa Ohira

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Background

Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-β superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC.

Methods

MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT–PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated.

Results

MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT–PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median.

Conclusions

MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.
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Metadata
Title
Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis
Authors
Mitsuru Sugimoto
Rei Suzuki
Yoshihiro Nozawa
Tadayuki Takagi
Naoki Konno
Hiroyuki Asama
Yuki Sato
Hiroki Irie
Jun Nakamura
Mika Takasumi
Minami Hashimoto
Tsunetaka Kato
Ryoichiro Kobashi
Osamu Suzuki
Yuko Hashimoto
Takuto Hikichi
Hiromasa Ohira
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02668-x

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