Subsite heterogeneity in the profiles of circulating cytokines in colorectal cancer

Abstract

Colorectal cancers (CRCs) are treated as one entity but are in fact a heterogeneous group of diseases. If not addressed, subsite-associated variability may interfere with mechanism-targeted therapies and accuracy of potential CRC biomarkers. Little is known about the contribution of systemic inflammatory and immune mediators to subsite heterogeneity in CRC. Our purpose was to compare the profiles of key cytokines between right and left colonic and rectal CRCs. Using Luminex xMAP® technology, serum concentrations of eotaxin, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, IFNγ, IP-10, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α and β, PDGF-BB, RANTES, TNFα, and VEGF-A were determined in 104 CRC patients. We found the concentrations of IL-12(p70), IL-10, IL-1ra, IL-4, IL-6, IL-7, IL-8, G-CSF and TNFα to be significantly higher in right-sided and GM-CSF in left-sided than rectal CRCs. The concentrations of IFNγ and MIP-1α were significantly higher in right-sided CRCs as compared to cancers of other locations combined. In turn, MIP-1β was higher in rectal CRCs as compared to colon cancers. Taken together, our results show subsite heterogeneity of CRC cancers in terms of systemic inflammatory and immune responses that ought to be taken into account when attempting immunotherapy or developing biomarkers. Additionally, more pronounced TH2 response accompanied by TH1 immunity and more prominent tumor-promoting inflammation in CRC patients with primary tumors originating from right-sided colon may constitute a molecular background of unfavorable prognosis associated with this location.