Elevated expression of macrophage migration inhibitory factor correlates with tumor recurrence and poor prognosis of patients with gliomas

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Abstract
Macrophage migration inhibitory factor (MIF) plays a critical role in tumorigenesis. We aim to examine the association of MIF with tumor recurrence and survival of gliomas, and to determine whether MIF is a valuable prognostic predictor for glioma patients. The expression of MIF and interleukin 8 (IL-8) was evaluated in 36 high-grade gliomas (20 glioblastoma multiforme, 13 anaplastic astrocytoma, and 3 anaplastic oligoastrocytoma) and 32 low-grade gliomas (18 fibrillary astrocytoma, 5 pilocytic astrocytoma, 5 oligodendroglioma, 3 ependymoma and 1 pleomorphic xanthoastrocytoma) by immunostaining. Intratumoral microvessel density (IMD) of tumors in relation to immunostainings and clinicopathological factors were analyzed statistically as well as the follow-up data of patients. High expression of both MIF (58.8%) and IL-8 (52.9%) was significantly associated with high-grade gliomas and increased microvessels in tumors, but only high expression of MIF was closely related to tumor recurrence (P = 0.001). High expression of IL-8 exhibited a close correlation with high expression of MIF in tumors (P = 0.001). Histological grading, high expression of MIF and IL-8 correlated with patients’ overall survival in univariate analysis. However, only histological grading and MIF expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis; the hazard ratios were 28.012 (P = 0.001) and 11.782 (P = 0.001), respectively. Elevated production of MIF in glioma tumor cells may contribute to tumor recurrence and a worse prognosis. MIF may serve as an independent predictive factor for prognosis of glioma patients.

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