Chen I-Chien, Lee Kuen-Haur, Hsu Ying-Hua, Wang Wei-Ran, Chen Chuan-Mu, Cheng Ya-Wen
Department of Life Sciences and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan.
Dis Markers. 2016;2016:8169724. doi: 10.1155/2016/8169724. Epub 2016 Aug 8.
Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host's immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of the APC gene remains unknown. Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci. Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate of APC. Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate of APC, making IDO1 an interesting target for immunotherapy in CRC.
目的。癌细胞利用吲哚胺2,3-双加氧酶1(IDO1)途径抑制宿主免疫反应,以促进恶性细胞的存活、生长、侵袭和转移。研究表明,较高的IDO1表达与结直肠癌(CRC)进展相关,并与临床预后不良相关。然而,APC基因低突变率的CRC人群中IDO1表达之间的潜在相关性仍不清楚。材料与方法。收集192例CRC患者的组织和血液样本。采用免疫组织化学法分析IDO1、色氨酸2,3-双加氧酶(TDO2)和β-连环蛋白的表达。通过微卫星位点的PCR扩增确定微卫星不稳定性(MSI)。结果。结果显示,高IDO1或TDO2蛋白表达与CRC更具侵袭性表型的特征相关。他们还首次揭示了APC低突变率的CRC人群中,β-连环蛋白的异常表达与IDO1或TDO2蛋白之间存在正相关。结论。我们得出结论,IDO1调节的分子途径导致APC低突变率的CRC患者细胞核/细胞质中β-连环蛋白异常表达,使IDO1成为CRC免疫治疗的一个有吸引力的靶点。