IDO1/COX2 Expression Is Associated with Poor Prognosis in Colorectal Cancer Liver Oligometastases

Overview

Journal J Pers Med

Date 2023 Mar 29

PMID 36983678

Authors

Miaoqing Wu

Xiaoliang Wu

Xing Wang

Xiangchan Hong

Yifan Liu

Guangzhao Lv

Cong Li

Zhizhong Pan

Rongxin Zhang

Gong Chen

Affiliations

Soon will be listed here.

Abstract

Background: IDO1 and COX2 have emerged as promising immunotherapy targets. It is unclear whether IDO1 and COX2 expression levels in colorectal cancer (CRC) patients with liver oligometastases could be independent predictors of overall survival (OS) and progression-free survival (PFS). The purpose of this study was to investigate the correlation of IDO1 and COX2 expression levels with OS and PFS in CRC patients with liver oligometastases.

Methods: The expression levels of IDO1 and COX2 were assessed by immunohistochemistry in 107 specimens from patients with liver oligometastases. The correlation between the expression of IDO1 and COX2 and the clinicopathological parameters and OS/PFS in patients was examined.

Results: The expression level of IDO1/COX2 was significantly correlated with age and was not associated with gender, BMI, T stage, N stage, primary tumor size, liver metastasis size, CEA, CA19-9, CD3 TILs or CD8 TILs. In univariate analysis, we found that IDO1/COX2 expression, CEA and N stage all yielded significantly poor OS and PFS outcomes. In our multivariate Cox model, IDO1/COX2 coexpression, CEA and N stage were found to be significantly correlated with OS; IDO1/COX2 coexpression and CEA were significantly correlated with PFS.

Conclusions: IDO1/COX2 coexpression plays a pivotal role and may act as a potential prognostic biomarker for survival in CRC patients with liver oligometastases.

Citing Articles

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References

Zhou H, Liu Z, Wang Y, Wen X, Amador E, Yuan L . Colorectal liver metastasis: molecular mechanism and interventional therapy. Signal Transduct Target Ther. 2022; 7(1):70. PMC: 8897452. DOI: 10.1038/s41392-022-00922-2. View

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

Tomlinson J, Jarnagin W, DeMatteo R, Fong Y, Kornprat P, Gonen M . Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007; 25(29):4575-80. DOI: 10.1200/JCO.2007.11.0833. View

Wissniowski T, Hansler J, Neureiter D, Frieser M, Schaber S, Esslinger B . Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res. 2003; 63(19):6496-500. View

Dromi S, Walsh M, Herby S, Traughber B, Xie J, Sharma K . Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology. 2009; 251(1):58-66. PMC: 2663580. DOI: 10.1148/radiol.2511072175. View

Akgul O, Cetinkaya E, Ersoz S, Tez M . Role of surgery in colorectal cancer liver metastases. World J Gastroenterol. 2014; 20(20):6113-22. PMC: 4033450. DOI: 10.3748/wjg.v20.i20.6113. View

Takamatsu M, Hirata A, Ohtaki H, Hoshi M, Ando T, Ito H . Inhibition of indoleamine 2,3-dioxygenase 1 expression alters immune response in colon tumor microenvironment in mice. Cancer Sci. 2015; 106(8):1008-15. PMC: 4556390. DOI: 10.1111/cas.12705. View

Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C . Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res. 2006; 12(4):1144-51. DOI: 10.1158/1078-0432.CCR-05-1966. View

Zhou Q, Han H, Lu J, Liu T, Huang K, Deng C . Up-regulation of indoleamine 2,3-dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients. Cancer Commun (Lond). 2020; 40(1):3-15. PMC: 7163927. DOI: 10.1002/cac2.12001. View

10.

Chalabi M, Fanchi L, Dijkstra K, van den Berg J, Aalbers A, Sikorska K . Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020; 26(4):566-576. DOI: 10.1038/s41591-020-0805-8. View

11.

Dahlin A, Henriksson M, van Guelpen B, Stenling R, Oberg A, Rutegard J . Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor. Mod Pathol. 2011; 24(5):671-82. DOI: 10.1038/modpathol.2010.234. View

12.

Rosenbaum M, Gigliotti B, Pai S, Parangi S, Wachtel H, Mino-Kenudson M . PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma. Endocr Pathol. 2018; 29(1):59-67. PMC: 6500591. DOI: 10.1007/s12022-018-9514-y. View

13.

Ino K, Yoshida N, Kajiyama H, Shibata K, Yamamoto E, Kidokoro K . Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer. Br J Cancer. 2006; 95(11):1555-61. PMC: 2360726. DOI: 10.1038/sj.bjc.6603477. View

14.

Ma W, Wang X, Yan W, Zhou Z, Pan Z, Chen G . Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer. World J Gastroenterol. 2018; 24(20):2181-2190. PMC: 5974580. DOI: 10.3748/wjg.v24.i20.2181. View

15.

Gogna S, Goyal P . Recent Strategies and Paradigm Shift in Management of Hepatic Metastasis from Colorectal Cancer. Indian J Surg Oncol. 2018; 9(4):456-460. PMC: 6265191. DOI: 10.1007/s13193-018-0766-2. View

16.

Valderrama-Trevino A, Barrera-Mera B, Ceballos-Villalva J, Montalvo-Jave E . Hepatic Metastasis from Colorectal Cancer. Euroasian J Hepatogastroenterol. 2017; 7(2):166-175. PMC: 5670263. DOI: 10.5005/jp-journals-10018-1241. View

17.

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

18.

Theate I, van Baren N, Pilotte L, Moulin P, Larrieu P, Renauld J . Extensive profiling of the expression of the indoleamine 2,3-dioxygenase 1 protein in normal and tumoral human tissues. Cancer Immunol Res. 2014; 3(2):161-72. DOI: 10.1158/2326-6066.CIR-14-0137. View

19.

Platten M, von Knebel Doeberitz N, Oezen I, Wick W, Ochs K . Cancer Immunotherapy by Targeting IDO1/TDO and Their Downstream Effectors. Front Immunol. 2015; 5:673. PMC: 4290671. DOI: 10.3389/fimmu.2014.00673. View

20.

Hennequart M, Pilotte L, Cane S, Hoffmann D, Stroobant V, De Plaen E . Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance. Cancer Immunol Res. 2017; 5(8):695-709. DOI: 10.1158/2326-6066.CIR-16-0400. View