Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma

Abstract

Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial–mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT‐related genes and transcription factors are associated with poor prognosis in ccRCC. EMT‐related factors suppress E‐cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), β‐catenin, and E‐cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan–Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm‐c levels compared to those with low MIFn and MIFm‐c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced‐stage ccRCC.

Keywords

• EMT
• epithelial–mesenchymal transition
• MIF
• macrophage migration inhibitory factor
• ccRCC
• clear cell renal cell carcinoma