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Expression Pattern and Clinicopathological Relevance of the Indoleamine 23-Dioxygenase 1/Tryptophan 23-Dioxygenase Protein in Colorectal Cancer

机译:吲哚胺23-双加氧酶1 /色氨酸23-双加氧酶蛋白在大肠癌中的表达规律及临床病理意义

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摘要

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.
机译:目的癌细胞使用吲哚胺2,3-二加氧酶1(IDO1)途径抑制宿主的免疫反应,以促进恶性细胞的存活,生长,侵袭和转移。已证明较高的IDO1表达与大肠癌(CRC)进展有关,并且与临床结果受损相关。然而,在具有低APC基因突变率的CRC人群中IDO1的表达之间的潜在相关性仍然未知。材料与方法。从192名CRC患者中收集组织和血液样本。通过免疫组织化学分析IDO1,色氨酸2,3-双加氧酶(TDO2)和β-catenin蛋白的表达。通过微卫星基因座的PCR扩增确定微卫星不稳定性(MSI)。结果。结果表明,IDO1或TDO2蛋白的高表达与CRC更具侵略性的表型有关。他们还首次揭示了APC突变率低的CRC人群中β-catenin的异常表达与IDO1或TDO2蛋白之间呈正相关。结论。我们得出的结论是,IDO1调控的分子途径导致APC突变率低的CRC患者的细胞核/细胞质中β-catenin的异常表达,使IDO1成为CRC免疫治疗的一个有趣目标。

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