Artikel
Intrinsic Angiostatic Immune Reaction in Colorectal Carcinoma: Implications for Patient´s Survival and Antiangiogenic Therapy
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Veröffentlicht: | 16. April 2008 |
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Gliederung
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Introduction: Angiogenesis and inflammation are the two major stroma reactions in colorectal carcinoma (CRC). Guanylate binding protein-1 (GBP-1) is a key mediator of inflammation-associated angiostasis. Therefore, we hypothesized that GBP-1 expression may indicate intrinsic angiostasis and may be associated with an improved outcome in CRC patients.
Materials and methods: Affymetrix microarray analyses, RT-PCR, multiplex RT-PCR for simultaneous detection of GBP-1, CXCL9, CXCL10, CXCL11, immunohistochemical detection of GBP-1 in CRC tissue arrays.
Results: 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.
Conclusion: Our results indicated that GBP-1 is a novel biomarker and an active component of a Th-1-like angiostatic immune reaction (IAR). IAR in CRC is beneficial for the patient´s cancer-related survival and the identification of tumors with IAR may provide a novel criterion for patient selection to improve response rates to antiangiogenic therapy. Induction of IAR may be a promising approach for the clinical treatment of CRC.