Abstract
Abstract Background: The prognostic value of many circulating cytokines in metastatic colorectal cancer (CRC) patients is undetermined. By using high through-put approach, this study was to evaluate the prognostic values of circulating cytokines in patients with metastatic CRC and identify potential therapeutic targets. Methods: Thirty-nine cytokines were simultaneously analyzed in serum samples from 99 patients with metastatic CRC by using multiplex bead-based Luminex technology. Three CRC cell lines, together with three more aggressive lines derived from them, were used to validate three potential therapeutic targets by applying neutralizing antibodies. Results: Elevated levels of 17 cytokines were found to be significant risk factors for the overall survival (OS) of patients. Only macrophage-derived chemokine (MDC) positively correlated with better prognosis. Interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), MCP-3 and MDC were significant independent predictor of OS in multivariate analyses. The risk scoring system developed by combining IL-8, MCP-1, MCP-3, and MDC, was more effective than each individual factor to predictor the OS. IL-8 was secreted by three CRC cell lines, with higher expression observed in more-aggressive cells. Blocking of IL-8 with a neutralizing antibody inhibited the invasiveness of CRC cells. MCP-1 and MCP-3 were secreted by SW480 cell line, with higher expression in more-aggressive cell. Neutralizing antibodies against MCP-1 or MCP-3 significantly inhibited the cellular invasion. Conclusions: The serum levels of 18 cytokines correlated with the prognosis of metastatic CRC patinets. Among them, IL-8, MCP-1, MCP-3 and MDC were independent prognostic factors for OS. IL-8, MCP-1, and MCP-3 are potential therapeutic targets in CRC. Citation Format: Zhi-Yuan Chen, Wen-Zhuo He, Li-Xia Peng, Rong-Ping Guo, Liang-Ping Xia, Chao-Nan Qian. Serum cytokine profiling in metastatic colorectal cancer patients: IL-8, MCP-1, and MCP-3 are theranostic targets. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1225. doi:10.1158/1538-7445.AM2013-1225
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