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Introduction: It has been shown that the proangiogenic proteins angiogenin (ANG) and interleukin-8 (IL8) are produced by endothelial cells (EC), fibroblasts and peripheral blood cells. Also, some colon, breast, and prostate cancers have been shown to over express ANG and IL8. EC surface actins are receptors for ANG; the binding of ANG to actin on EC's promotes degradation of the basement membrane which facilitates EC migration, an essential early step in angiogenesis. EC's also express the IL-8 receptors CXCR1 and CXCR2; tumor derived IL8, via binding to these receptors, in an autocrine fashion, enhances tumor cell proliferation and survival and also promotes pathologic angiogenesis. IL8's pro-angiogenic effects are independent of VEGF. Plasma ANG and IL8 levels in patients with colorectal cancer (CRC) have not been well studied. This study's purpose was to compare preoperative (PreOp) plasma ANG and IL8 levels in patients with CRC and benign colonic diseases (BCD).
Method: Patients undergoing colorectal resection for CRC or BCD prospectively enrolled in an IRB approved tissue/data bank, for whom PreOp plasma was available, were studied. Clinical, operative and pathologic data were collected. Plasma ANG (ng/ml) and IL8 (pg/ml) levels were determined via ELISA in duplicate and reported as median 95%CI. Levels between groups were compared by the Mann- Whitney test (significance p<0.05).
Results: A total of 122 CRC (66% colon, 34% rectal) and 96 BCD (adenoma 50%, diverticulitis 47%, other 3%) patients were included. Plasma stores (PreOp samples) did not permit both assays to be done for all patients. In regards to ANG, 86 CRC and 80 BCD patients were studied while the IL8 assay included 73 CRC and 62 BCD patients. The median PreOp CRC ANG level (ng/ml) (339.9, CI: 339.6, 373.2) was significantly higher than the BCD group result (295.6, CI: 276.0, 306.6; p<0.0001). Similarly, for IL8, the median PreOp CRC level (pg/ml) (17.3, CI 17.8, 22.8) was higher than the BCD groups outcome (14.2, CI: 12.8, 16.8; p<0.001). Of note no correlation was found between ANG or IL8 plasma levels and cancer stage.
Conclusion: The median PreOp plasma ANG and IL8 levels in the CRC group were modestly increased (21-25%) vs. the BCD patients. ANG and IL8 shed from tumors expressing these proteins may be responsible for the increase. Alternate sources may be neovascularization and inflammation at the tumor site. Further study of larger groups with concomitant tumor analysis would help determine the clinical relevance, if any, of these changes, the source of the added protein and would better define the relationship between cancer stage and blood levels.