Purpose: There is currently no adequate biomarker for predicting colorectal cancer (CRC) recurrence. Chemokine (C–C motif) ligand 2 (CCL2) induces macrophages and fibroblasts to occupy metastatic niches in distant organs. The purpose of this study was to examine CCL2 as a potential predictive biomarker for CRC recurrence. Methods: Plasma samples (n = 402) were collected from 80 stage II/III/IV CRC cases and the relationship between CCL2 profiles and recurrence was investigated. The tumor immune response genes associated with CCL2 mRNA expression in a subgroup of 8 stage I/II CRC cases with 12 recurrent sites and The Cancer Genome Atlas database were also analyzed retrospectively. Results: Sixteen stage II/III/IV postoperative recurrent CRC cases experienced a significant increase in plasma CCL2 levels 6 months after surgery and continuously increased even after R0-1 resection. The 6-month postoperative CCL2 levels in recurrent cases of ≥ 1 year were significantly higher than in non-recurrent cases and recurrent cases of < 1 year. The CCL2 level in the primary tumor cases significantly correlated with the cytolytic activity, thus indicating a tumor immune response from the CD163-expressing macrophages. Conclusion: Plasma CCL2 was found to be a predictive biomarker of postoperative CRC recurrence. CCL2 in metastatic sites derives from metastatic niches that surpass the host immune response.
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