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.
Conclusions
MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential 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.