期刊
INTERNATIONAL JOURNAL OF CANCER
卷 123, 期 9, 页码 2120-2129出版社
WILEY
DOI: 10.1002/ijc.23764
关键词
guanylate binding protein-1; interferon-gamma; colorectal carcinoma; angiogenesis; inflammation
类别
资金
- University of Erlangen-Nuremberg [AZ 05.06.05.1, AZ 03.09.22.1]
- Deutsche Forschungsgemeinschaft [STU 317/2-1, DFG-GK 1071]
- German Cancer Aid, Interdisciplinary Center for Clinical Research (IZKF) of the University of Erlangen-Nuremberg
Angiogenesis and inflammation are the 2 major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein-1 (GBP-1) is a key mediator of angiostatic effects of inflammation. Therefore, we hypothesized that GBP-1 may be a biomarker of intrinsic angiostasis associated with an improved outcome in CRC patients. GBP-1 was strongly expressed in endothelial cells and immune cells in the desmoplastic stroma of 32% of CRC as determined by immunohistochemical investigation of 388 sporadic CRC. Cancer-related 5-year survival was highly significant (p < 0.001) increased (16.2%) in patients with GBP-1-positive CRC. Multivariate analysis showed that GBP-1 is an independent prognostic factor indicating a reduction of the relative risk of cancer-related death by the half (p = 0.032). A comparative transcriptome analysis (22,215 probe sets) of GBP-1-positive (n = 12) and -negative (n = 12) tumors showed that particularly IFN-gamma-induced genes including the major antiangiogenic chemokines CXCL9, CXCL10 and CXCL11 were coexpressed with GBP1. Altogether our findings indicated that GBP-1 may be a novel biomarker and an active component of a Th-1-like angiostatic immune reaction in CRC. This reaction may affect patient's response to antiangiogenic therapy and the identification of such tumors may provide a novel criterion for patient selection. Moreover, the induction of a Th-1-like angiostatic immune reaction may be a promising approach for the clinical treatment of CRC. (c) 2008 Wiley-Liss, Inc.
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