Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

doi:10.3748/wjg.v24.i20.2181

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World Journal of Gastroenterology

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World J Gastroenterol. May 28, 2018; 24(20): 2181-2190
Published online May 28, 2018. doi: 10.3748/wjg.v24.i20.2181

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

Wen-Juan Ma, Xing Wang, Wen-Ting Yan, Zhong-Guo Zhou, Zhi-Zhong Pan, Gong Chen, Rong-Xin Zhang

Wen-Juan Ma, Zhong-Guo Zhou, Zhi-Zhong Pan, Gong Chen, Rong-Xin Zhang, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China

Wen-Juan Ma, Zhong-Guo Zhou, Zhi-Zhong Pan, Gong Chen, Rong-Xin Zhang, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, Guangdong Province, China

Xing Wang, Wen-Ting Yan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, Hubei Province, China

Zhong-Guo Zhou, Department of Hepatobiliary Surgery, Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China

Zhi-Zhong Pan, Gong Chen, Rong-Xin Zhang, Department of Colorectal Surgery, Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China

Author contributions: All authors helped to perform the research; Ma WJ performed the manuscript writing, experimental procedures and data analysis; Wang X performed the experiments and data analysis; Yan WT contributed to writing of the manuscript and data analysis; Zhou ZG contributed to collecting data and study design; Pan ZZ contributed to data analysis and study design; Chen G contributed to writing of the manuscript and drafting of the study conception; Zhang RX contributed to study design and data analysis.

Supported by the National Natural Science Foundation of China, No. 81502459.

Institutional review board statement: This study was approved by the Sun Yat-sen University Cancer Center Institutional Review Board and Human Ethics Committee.

Informed consent statement: Informed consent was obtained from all individual participants included in the study.

Conflict-of-interest statement: We declare that there is no conflict of interest in this study.

Data sharing statement: No additional data are available.

Correspondence to: Rong-Xin Zhang, MD, Attending Doctor, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Dongfeng East Road No. 651, Guangdong 510060, Guangzhou Province, China. zhangrx@sysucc.org.cn

Telephone: +86-20-87343584 Fax: +86-20-87343584

Received: February 28, 2018
Peer-review started: February 28, 2018
First decision: March 15, 2018
Revised: March 21, 2018
Accepted: April 16, 2018
Article in press: April 15, 2018
Published online: May 28, 2018
Processing time: 89 Days and 3.2 Hours

ARTICLE HIGHLIGHTS

Research background

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Because of genetic mutations and environmental factors, CRC development is a very complex process and is determined by multistage factors. Currently, immunotherapy has become one of the most promising treatments for CRC. However, whether indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 (IDO1/COX2) coexpression is correlated with overall survival (OS) in CRC patients remains unknown.

Research motivation

CRC has demonstrated high heterogeneity in recent years. Recent studies have demonstrated that IDO1 can suppress the T cell response to tumors. A selective COX2 inhibitor, celecoxib, could improve chemosensitivity when CRC cells are exposed to the combination of 5-FU and CPT-11 and could reduce hand-foot syndrome induced by capecitabine. In this study, we conducted a retrospective analysis for the potential prognostic importance of the correlation of IDO1 and COX2 in survival outcome prognosis, including their coexpression, cytoplasmic and nuclear localization of IDO1, and tumor-infiltrating lymphocytes.

Research objectives

This study aimed to clarify the potential significance of IDO1/COX2 as a prognostic biomarker in CRC in vitro.

Research methods

Immunohistochemical staining of IDO1 and COX2 was performed in a clinical cohort consisting of 96 CRC cases. Expression of IDO1 and COX2 was correlated with clinicopathological indicators and the clinical outcome of CRC patients.

Research results

In the CRC group, combined cytoplasmic IDO1/COX2 coexpression analysis yielded a stronger predictor index, with hazard ratio (HR) = 2.218 (95% confidence interval (CI): 1.011-4.48, P = 0.047) in the IDO1^High/COX2^High group, and tumor differentiation was significantly correlated with OS (HR = 3.473, 95%CI: 1.201-10.046, P = 0.022) but not nuclear IDO1, cytoplasmic IDO1, nor combined nuclear IDO1/COX2 expression. Our results revealed that cytoplasmic IDO1/COX2 coexpression and tumor differentiation were independent predictors for poor OS in CRC.

In the CRC celecoxib subgroup, combined cytoplasmic IDO1/COX2 coexpression analysis yielded a stronger predictor index, with HR = 3.210 (95%CI: 1.074-9.590, P = 0.037) in the IDO1^High/COX2^High group, and tumor differentiation was significantly correlated with OS (HR = 11.962, 95%CI: 1.526-23.787, P = 0.018) but not nuclear IDO1, cytoplasmic IDO1, nor combined nuclear IDO1/COX2 expression.

Research conclusions

The results of the current study demonstrate that the coexpression of cytoplasmic IDO1 and COX2 plays a key role in survival prognosis in CRC patients.

Research perspectives

IDO1 could be a novel therapeutic target for human CRC, especially as a biotarget of immunotherapy.