Expression and Prognostic Value of Indoleamine 2,3-dioxygenase in Pancreatic Cancer

被引:44
作者
Zhang, Tao [1 ]
Tan, Xiang-Long [1 ]
Xu, Yong [1 ]
Wang, Zi-Zheng [1 ]
Xiao, Chao-Hui [1 ]
Liu, Rong [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Chinese Peoples Liberat Army Med Sch, Dept Hepatobiliary & Pancreat Surg Oncol, 28 Fuxing Rd, Beijing 100853, Peoples R China
关键词
Immunohistochemistry; Indoleamine 2,3-dioxygenase; Pancreatic Neoplasms; Prognosis; DENDRITIC CELLS; 2,3 DIOXYGENASE; BREAST-CANCER; IDO; 3-DIOXYGENASE; STATISTICS;
D O I
10.4103/0366-6999.201613
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. Methods: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-gamma (IFN-gamma). We performed immunohistochemical staining and Western blot analysis for IDO expression in both pancreatic cancer and normal pancreas tissues obtained from Chinese PLA General Hospital from July 2012 to December 2013. Survival analysis was performed to correlate IDO expression and histopathologic parameters with overall survival. The Kaplan-Meier method and Cox proportional hazards regression model were conducted. Results: PANC-1, CFPAC-1, and BxPC-3 cell lines expressed IDO at the protein level, and the relative expression amount increased after stimulation with 500 U/ml IFN-gamma. Immunohistochemical analysis results revealed that high IDO expression was observed in 59% of pancreatic adenocarcinoma tissues. Compared with normal pancreatic tissues, pancreatic adenocarcinoma showed significantly higher IDO expression levels, especially among patients with high tumor node metastasis (TNM) stages (chi(2) = 4.550, P = 0.030), poor histological differentiation (chi(2) = 5.690, P = 0.017), and lymph node metastasis (chi(2) = 4.340 P = 0.037). Kaplan-Meier survival curves showed that high IDO expression was correlated with low survival rates (hazard ratio [HR] = 0.49 P = 0.009). Multivariate analysis using Cox proportional hazards model indicated that lymph node metastasis (HR = 0.35 P = 0.010) and IDO expression (HR = 0.42 P = 0.020) were two independent prognostic predictors of pancreatic adenocarcinoma. Conclusions: The study confirmed that high IDO expression in pancreatic adenocarcinoma was related to poor prognosis of patients. These findings provided evidence that IDO was involved in pancreatic adenocarcinoma progression and might serve as a relevant therapeutic target.
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页码:710 / 716
页数:7
相关论文
共 31 条
[1]   Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma [J].
Ben-Haj-Ayed, Ahlem ;
Moussa, Adnene ;
Ghedira, Randa ;
Gabbouj, Sallouha ;
Miled, Souad ;
Bouzid, Nadia ;
Tebra-Mrad, Sameh ;
Bouaouina, Noureddine ;
Chouchane, Lotfi ;
Zakhama, Abdelfattah ;
Hassen, Elham .
IMMUNOLOGY LETTERS, 2016, 169 :23-32
[2]   Analysis of Indoleamine 2-3 Dioxygenase (IDO) and EGFR Co-expression in Breast Cancer Tissue by Immunohistochemistry [J].
Bi, Wei-Wei ;
Zhang, Wei-Hua ;
Yin, Gui-Hua ;
Luo, Hong ;
Wang, Shou-Qin ;
Wang, Hongran ;
Li, Chao ;
Yan, Wei-Qun ;
Nie, De-Zhi .
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (14) :5535-5538
[3]   The role of plasma IDO activity as a diagnostic marker of patients with colorectal cancer [J].
Cavia-Saiz, M. ;
Muniz Rodriguez, P. ;
Llorente Ayala, B. ;
Garcia-Gonzalez, M. ;
Coma-del Corral, M. J. ;
Garcia Giron, C. .
MOLECULAR BIOLOGY REPORTS, 2014, 41 (04) :2275-2279
[4]   Cancer statistics: updated cancer burden in China Preface [J].
Chen, Wanqing .
CHINESE JOURNAL OF CANCER RESEARCH, 2015, 27 (01) :1-1
[5]   Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies [J].
Chiorean, Elena Gabriela ;
Coveler, Andrew L. .
DRUG DESIGN DEVELOPMENT AND THERAPY, 2015, 9 :3529-3545
[6]   Effect of Splenic Regulatory T-cell Apoptosis on the Postresuscitation Immune Dysfunction in a Porcine Model [J].
Gu, Wei ;
Zhang, Qian ;
Li, Chun-Sheng .
CHINESE MEDICAL JOURNAL, 2016, 129 (13) :1577-1583
[7]   Indoleamine 2,3-Dioxygenase and Dendritic Cell Tolerogenicity [J].
Harden, Jamie L. ;
Egilmez, Nejat K. .
IMMUNOLOGICAL INVESTIGATIONS, 2012, 41 (6-7) :738-764
[8]   Dendritic Cells, Indoleamine 2,3 Dioxygenase and Acquired Immune Privilege [J].
Huang, Lei ;
Baban, Babak ;
Johnson, Burles A., III ;
Mellor, Andrew L. .
INTERNATIONAL REVIEWS OF IMMUNOLOGY, 2010, 29 (02) :133-155
[9]   Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy [J].
Inaba, Tomoko ;
Ino, Kazuhiko ;
Kajiyamaa, Hiroaki ;
Shibata, Kiyosumi ;
Yamamoto, Eiko ;
Kondo, Shinji ;
Umezu, Tomokazu ;
Nawa, Akihiro ;
Takikawa, Osamu ;
Kikkawa, Fumitaka .
GYNECOLOGIC ONCOLOGY, 2010, 117 (03) :423-428
[10]   IDO is highly expressed in breast cancer and breast cancer-derived circulating microvesicles and associated to aggressive types of tumors by in silico analysis [J].
Isla Larrain, M. T. ;
Rabassa, M. E. ;
Lacunza, E. ;
Barbera, A. ;
Creton, A. ;
Segal-Eiras, A. ;
Croce, M. V. .
TUMOR BIOLOGY, 2014, 35 (07) :6511-6519