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

Abstract

Monocyte chemotactic protein-1 (MCP-1/CCL2) and macrophage inflammatory protein-1α (MIP-1α/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.

CCL2/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma

“…As a potent monocyte/macrophage chemotactic factor, CCL2 enhanced metastases in numerous tumors by recruiting macrophages [24, 25]. Recently, the elevated expression of CCL2 was also reported in HNSCC with a poor outcome in patients [26]. Blockade of CCL2/CCR2 axis in various tumors displayed remarkable therapeutic effects as the versatile functions of macrophages in tumor progression [10].…”

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

“…However, there are also reports that increased expression of CCL2 in tumor tissue is associated with better prognosis: These studies include patients with gastric cancer [59], colorectal cancer [76], liver cancer [77], and non-small cell lung cancer [78]. There are also a number of studies, that report either that serum CCL2 levels in cancer patients are not related to clinical variables or that higher [53], and Tonouchi et al [59] report that serum CCL2 levels were decreased in patients with astrocytic brain tumors, oral squamous cell carcinoma, and gastric cancer, and Tonouchi et al report CCL2 levels tended to decrease in accordance with disease progression and that decreased serum CCL2 levels was associated with poor survival. Dehqanzada et al [52] report that elevated serum CCL2 levels correlated with favorable prognostic variables in patients with breast cancer, and Farren et al [54] report that elevated serum CCL2 levels correlated with increased survival in pancreas cancer patients.…”

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

“…The results of studies in other neoplasms provide inconsistent data. Ding et al [24] noted significantly lower MCP-1 and CCL3 serum concentrations in patients with oral squamous cell carcinoma and leukoplakia. Similar results were obtained for ovarian and colorectal cancer [25–27].…”