CCL18 overexpression predicts a worse prognosis in oral squamous cell carcinoma (OSCC)

Lisha Mao, Rui Zhuang, Lizheng Qin, Zhengxue Han, xin huang, Renji Chen, Ying Su, Lihua Ge, Jing Yang,  Jun Li,  Xuejiu Wang

Abstract:

Oral squamous cell carcinoma (OSCC) presents severe morbidity and high mortality owing to local recurrence or remote metastasis. Molecular markers, including chemokines, might provide more efficient prognostic information or even therapeutic targets for the treatment of OSCC. Using quantitative RT-qPCR, we found that CCL18 was dramatically overexpressed in 30 OSCC tissues at the mRNA level in comparison with their adjacent non-cancerous oral mucosa tissues and 15 oral mucosa tissues from non-malignant patients. We then analyzed the relationship between CCL18 overexpression and patient clinical characters and outcomes using immunohistochemistry staining (IHC) in 102 paired OSCC cancerous and adjacent non-cancerous tissues; the increase in CCL18 expression was significantly higher in male patients (p=0.047), tumors of the palate and floor of the mouth (p=0.014), patients with positive lymph node metastasis (p=0.007), and patients with poor tumor differentiation (p=0.029). The median overall survival time and time-to-recurrence were 80.6 and 61.4 months in patients with high CCL18 expression, respectively, as against 93.4 and 81.6 months in patients with comparatively lower CCL18 expression, respectively (p=0.033 and 0.012, respectively; log-rank test). Multivariate analyses indicated age, poor differentiation, and CCL18 levels to be independent prognostic factors for predicting both overall and disease-free survival time. Our study suggests that CCL18 is a novel candidate marker for the OSCC malignancy and prognosis, including lymph node metastasis, time-to-recurrence, and disease-free survival time.