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

Abstract
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.
AuthorsI-Chien Chen, Kuen-Haur Lee, Ying-Hua Hsu, Wei-Ran Wang, Chuan-Mu Chen, Ya-Wen Cheng
JournalDisease markers (Dis Markers) Vol. 2016 Pg. 8169724 ( 2016) ISSN: 1875-8630 [Electronic] United States
PMID27578919 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tryptophan Oxygenase
Topics
  • Aged
  • Biomarkers, Tumor (metabolism)
  • Colorectal Neoplasms (enzymology, pathology)
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
  • Lymphatic Metastasis
  • Male
  • Neoplasm Staging
  • Prognosis
  • Tryptophan Oxygenase (metabolism)

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