Prognostic role of macrophage migration inhibitory factor expression in patients with squamous cell carcinoma of the lung

Abstract

Background: Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the inflammatory and immune response in squamous cell carcinoma (SCC). Recent studies have reported that MIF is involved in the tumorigenesis and overexpressed in various cancers. In this study, we assessed the prognostic role of MIF expression in SCC of the lung, and demonstrated the effect of knockdown of MIF on the migration in lung SCC cell lines. Methods: The relationship between MIF expression and clinicopathological parameters and the prognostic role of MIF expression were evaluated with immunohistochemical staining in 96 patients with SCC of the lung. The expression of MIF mRNA and protein was analyzed by semi-quantitative polymerase chain reaction and Western blot in lung SCC cell. The effect of knockdown of MIF was assessed by wound healing assay. Results: The high percentage of MIF-positive cells was significantly associated with lymph node metastasis (P = 0.004), and was a poor prognostic factor of disease-free survival (DFS) (hazard ratio [HR]: 3.125; 95% confidence interval [CI], 1.628–5.998; P = 0.001) and disease-specific survival (DSS) (HR: 2.303; 95% CI, 1.172–4.525; P = 0.016). Moreover, Kaplan-Meier analysis showed that SCC patients with a high percentage of MIF-positive cells had a significantly lower DFS (P = 0.001) and DSS (P = 0.014) than those with a low percentage. Furthermore, wound healing assay revealed that knockdown of MIF resulted in decreased cellular migration. Conclusion: MIF is closely associated with tumor progression and could be a prognostic factor in SCC of the lung.