巨噬细胞抑制细胞因子-1对胆管癌的临床实用性及促进作用：一项实验性生物标志物分析

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

作者信息

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

机构信息

Department of Gastroenterology, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Department of Pathology, Shirakawa Kousei General Hospital, Shirakawa, Japan.

出版信息

Cancer Cell Int. 2022 Aug 10;22(1):250. doi: 10.1186/s12935-022-02668-x.

DOI:10.1186/s12935-022-02668-x

PMID:35948981

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9367137/

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.

摘要

背景

胆管癌（BTC）预后较差；因此，需要有用的生物标志物和治疗方法。巨噬细胞抑制细胞因子-1（MIC-1）是转化生长因子-β超家族的成员，在胰胆管癌患者中血清水平升高。然而，MIC-1对BTC的影响尚不清楚。因此，我们研究了MIC-1对BTC的影响，并评估MIC-1是否为BTC的生物标志物或治疗靶点。

方法

通过组织学免疫染色、组织芯片（TMA）、蛋白质印迹法和逆转录PCR（RT-PCR）检测BTC细胞中MIC-1的表达。进行细胞培养实验以研究MIC-1对BTC细胞系（HuCCT-1和TFK-1）的影响。回顾性验证了118例胰胆管疾病患者（良性疾病患者作为对照组，n = 62；BTC患者，n = 56）血清MIC-1水平与疾病状态或凋亡标志物M30血清水平之间的关系。还研究了BTC最有效的诊断标志物。

结果

使用TMA、蛋白质印迹法和RT-PCR确定，在BTC组织标本中证实了MIC-1的表达，且BTC细胞中的表达高于正常胆管上皮细胞。在细胞培养实验中，MIC-1通过阻止凋亡增加了BTC细胞的增殖和侵袭，并抑制了吉西他滨的作用。在血清分析中，血清MIC-1水平与BTC进展和血清M30水平呈正相关。联合使用MIC-1和M30可提高早期或所有阶段诊断BTC的能力。血清MIC-1＜中位数的BTC患者的总生存期明显长于血清MIC-1≥中位数的BTC患者。