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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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
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 IDO1High/COX2High 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 IDO1High/COX2High 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.
