Yamada Mitsunari, Sakurai Toshiharu, Komeda Yoriaki, Nagai Tomoyuki, Kamata Ken, Minaga Kosuke, Yamao Kentaro, Takenaka Mamoru, Hagiwara Satoru, Matsui Shigenaga, Watanabe Tomohiro, Nishida Naoshi, Kashida Hiroshi, Kudo Masatoshi
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Oncology. 2017;93 Suppl 1:20-26. doi: 10.1159/000481225. Epub 2017 Dec 20.
Although the stem cell marker Bmi1 is overexpressed in many malignancies, its role in inflammation-associated cancer is unclear. Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD).
To assess the involvement of Bmi1 in the development of CAC, we analyzed the gene expression of colon tissues collected from 111 patients with IBD and CAC.
In the colonic mucosa of patients with ulcerative colitis, the expression of Bmi1 correlated significantly with the expression of inflammatory cytokines such as IL-6, IL-17, IL-23, and tumor necrosis factor α (TNF-α). In the colonic mucosa of patients with Crohn's disease, the expression of Bmi1 correlated significantly with the expression of TNF-α and IL-23. The expression of Bmi1 was enhanced in the colonic mucosae of refractory IBD, suggesting that Bmi1 expression might be related to increased cancer risk. In addition, patients with high Bmi1 expression showed significantly lower response rates upon subsequent anti-TNF-α therapy as compared to patients with low Bmi1 expression. In human CAC specimens, the expression of Bmi1 was upregulated in nontumor tissues as well as tumors.
Bmi1 expression is related to a refractory clinical course of IBD and upregulated in refractory IBD and CAC. Measurement of Bmi1 expression is a promising approach for the advanced treatment and personalized management of IBD patients.
尽管干细胞标志物Bmi1在许多恶性肿瘤中过表达，但其在炎症相关癌症中的作用尚不清楚。结肠炎相关癌症（CAC）由慢性肠道炎症引起，通常源于难治性炎症性肠病（IBD）。
为评估Bmi1在CAC发生发展中的作用，我们分析了从111例IBD和CAC患者收集的结肠组织的基因表达。
在溃疡性结肠炎患者的结肠黏膜中，Bmi1的表达与白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、白细胞介素-23（IL-23）和肿瘤坏死因子α（TNF-α）等炎性细胞因子的表达显著相关。在克罗恩病患者的结肠黏膜中，Bmi1的表达与TNF-α和IL-23的表达显著相关。Bmi1的表达在难治性IBD的结肠黏膜中增强，提示Bmi1表达可能与癌症风险增加有关。此外，与Bmi1低表达的患者相比，Bmi1高表达的患者在随后的抗TNF-α治疗中的缓解率显著更低。在人类CAC标本中，Bmi1的表达在非肿瘤组织以及肿瘤中均上调。
Bmi1表达与IBD的难治性临床病程相关，且在难治性IBD和CAC中上调。检测Bmi1表达是IBD患者进行高级治疗和个性化管理的一种有前景的方法。
