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

Abstract

AIM

To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 (IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer (CRC) patients.

METHODS

We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival (OS) outcomes.

RESULTS

The expression of nuclear IDO1 was significantly correlated with body mass index (P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1 (P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio (HR) = 2.044, 95% confidence interval (CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2 (HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2 (HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1 (P = 0.041), nuclear/cytoplasmic IDO1 (HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2 (HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC (HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients (HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).

CONCLUSION

Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

Keywords: Prognosis; Indoleamine-2,3-dioxygenase 1; Cyclooxygenase 2; Colorectal cancer

Core tip: It was reported that indoleamine-2,3-dioxygenase 1 (IDO1) is an inhibitory factor that suppresses the T cell response to tumors. In this study, we evaluated IDO1/cyclooxygenase 2 (COX2) expression as an independent prognostic biomarker for colorectal cancer (CRC) patients. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC patients and celecoxib subgroup patients. Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent predictor for poor overall survival in CRC.