Premium
Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy
Author(s) -
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,
Stürzl Michael
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23764
Subject(s) - colorectal cancer , cxcl9 , angiogenesis , immune system , chemokine , cxcl10 , biomarker , inflammation , cancer research , medicine , stroma , immunology , cancer , carcinoma , oncology , biology , immunohistochemistry , biochemistry
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‐γ‐induced genes including the major antiangiogenic chemokines CXCL9, CXCL10 and CXCL11 were coexpressed with GBP‐1. 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. © 2008 Wiley‐Liss, Inc.