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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancer Cell International, Vol 22, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 1475-2867
DOI: 10.1186/s12935-022-02668-x
Popis: 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
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