Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy

作者：Naschberger Elisabeth; Croner Roland S; Merkel Susanne; Dimmler Arno; Tripal Philipp; Amann Kerstin U; Kremmer Elisabeth; Brueckl Wolfgang M; Papadopoulos Thomas; Hohenadl Christine; Hohenberger Werner; Stuerzl Michael

来源：International Journal of Cancer, 2008, 123(9): 2120-2129.

DOI：10.1002/ijc.23764

• guanylate binding protein-1
• interferon-gamma
• colorectal carcinoma
• angiogenesis
• inflammation

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.

• 出版日期2008-11-1