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

I-Chien Chen,Wei-Ran Wang,Kuen-Haur Lee,Ya-Wen Cheng,Ying-Hua Hsu,Chuan-Mu Chen

doi:10.1155/2016/8169724

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.

Highlights

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide
The Expression of IDO1 and TDO2 Was Significantly Increased in CRC Tissues and Correlated with Lymph Node Metastasis and Tumor Stage of CRC. Both IDO1 and TDO2 triggered by an immune challenge can catalyze Trp to Kyn and start Kyn pathway [20]
The results showed that the expression level of IDO1 (Table 1)

Summary

Introduction

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. There are nearly one million cases of CRC diagnosis worldwide each year [1, 2]. The genetic influences in CRC progression occur at various points and include APC mutations in the early stages and mutations in tumor suppressor TP53 and oncogene KRAS during the later stages [5]. These mutations are thought to drive malignant epithelial transformation. Mutations inactivating the APC tumor suppressor gene are believed to be critical in the majority of colon adenomas and carcinomas [6]. In colorectal adenomas and carcinomas where both APC alleles are defective, destruction of the free pool of beta-catenin is impaired, and active beta-catenin accumulates in the cytoplasm and nucleus to reactivate Wnt/beta-catenin target genes in CRC [8]. Our previous study showed that mutation rate of the APC gene in CRC was 33.8% [9], which is close to the reported level in Asia [10, 11] but significantly

Methods

Results

Conclusion