Serum CCL2 and CCL3 as potential biomarkers for the diagnosis of oral squamous cell carcinoma

Monocyte chemotactic protein-1 (MCP-1/CCL2) and macrophage inflammatory protein-1 alpha (MIP-1 alpha/CCL3) are small chemotactic proteins that have been found in several kinds of tumor tissue samples and function as key regulators of cancer progression. However, the expression of CCL2 and CCL3 in serum samples of oral squamous cell carcinoma (OSCC) patients remains unknown. This study aimed to investigate the prognostic meaning of serum CCL2 and CCL3 in OSCC. The concentration of CCL2 and CCL3 was assessed by ELISA in serum of OSCC patients (n=98), leukoplakia patients (n=14), and healthy donors (n=27). The results showed that the concentration of CCL2 in the OSCC group was significantly lower compared to that in the healthy controls (67.81 vs. 108.1 pg/ml, P<0.0001). The CCL3 concentration was higher in leukoplakia patients than in OSCC patients and healthy donors (201.9 vs. 153.9 or 118.3 pg/ml, P<0.05). No significant difference in CCL3 concentration was observed between OSCC patients and healthy donors. However, the OSCC group clearly presented two subclusters, i.e., CCL3(LOW) and CCL3(HIGH) OSCC subclusters, in which the serum level of CCL3 was positively related to the tumor size. Interestingly, the ratio of CCL2/CCL3 in OSCC patients was correlated to TNM (tumor, node, metastasis), smoking habits, and differentiation. The receiver operating characteristic (ROC) curve suggests that serum CCL2 is a good diagnostic marker to discriminate OSCC patients from healthy people (cutoff value, 101.1 pg/ml) and the ratio of CCL2/CCL3 also is a good diagnostic marker to discriminate leukoplakia patients and CCL3(HIGH) OSCC patients from healthy people (cutoff values, 1.080 and 0.424, respectively). These results indicate that CCL2 and CCL3 are associated with progression of OSCC and may be potential biomarkers.