Expression Pattern and Clinicopathological Relevance of the Indoleamine 2,3-Dioxygenase 1/Tryptophan 2,3-Dioxygenase Protein in Colorectal Cancer

Disease Markers - Tập 2016 - Trang 1-9 - 2016
I-Chien Chen1, Kuen‐Haur Lee2,3, Ying-Hua Hsu2,4, Weiran Wang5, Chuan‐Mu Chen1, Ya‐Wen Cheng2,3
1Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
2Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan
3Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
4Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan
5Graduate Institute of Medical Sciences, Collage of Medicine, Taipei Medical University, Taipei 110, Taiwan

Tóm tắt

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 theAPCgene 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 ofAPC.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 ofAPC, making IDO1 an interesting target for immunotherapy in CRC.

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