Abstract
Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma–carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis.
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Abbreviations
- CRC:
-
Colorectal cancer
- CT:
-
Cycle threshold
- IBD:
-
Inflammatory bowel diseases
- IFN:
-
Interferon
- IHC:
-
Immunohistochemistry
- IL:
-
Interleukin
- LGD:
-
Lower-grade dysplasia
- HGD:
-
High-grade dysplasia
- HPF:
-
High-power fields
- MGD:
-
Moderate-grade dysplasia
- MVD:
-
Microvessel densities
- PCR:
-
Polymerase chain reaction
- SEM:
-
Mean of standard error
- Th:
-
T helper
- TNF:
-
Tumor necrosis factor
- TNM:
-
Tumor/node/metastasis
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Acknowledgments
This research was supported by grants from the Medical Research Program of Northern Norway Regional Health Authority (Grant No. SFP-44-04) and the National Natural Science Foundation of China (Grant No. 81071969).
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Cui, G., Qi, H., Gundersen, M.D. et al. Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer. Cancer Immunol Immunother 64, 181–190 (2015). https://doi.org/10.1007/s00262-014-1624-x
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DOI: https://doi.org/10.1007/s00262-014-1624-x