Macrophage migration inhibitory factor predicts an unfavorable outcome after transarterial chemoembolization for hepatic malignancies

Abstract

Transarterial chemoembolization (TACE) is a therapeutic option for patients with intermediatestage hepatocellular carcinoma (HCC) or metastatic liver cancers. Identifying those patients who particularly benefit from TACE remains challenging. Macrophage migration inhibitory factor (MIF) represents is an inflammatory protein described in liver cancer patients, but no data on its prognostic relevance in TACE patients exist. Here, we evaluate MIF serum concentrations as a Accepted ArticleThis article is protected by copyright. All rights reserved potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies.MIF serum concentrations were measured by multiplex immunoassay in n=50 patients (HCC: n=39, liver metastases: n=11) before and one day after TACE as well as in 51 healthy controls.Serum concentrations of MIF did not differ between patients and healthy controls. Interestingly, in the subgroup of patients with larger tumor size, significantly more patients had increased MIF concentrations. Patients with an objective tumor response to TACE therapy showed comparable concentrations of serum MIF compared to patients who did not respond. MIF concentrations at day 1 after TACE were significantly higher compared to baseline concentrations. Importantly, baseline MIF concentrations above the optimal cut-off value (0.625 ng/ml) turned out as a significant and independent prognostic marker for a reduced overall survival (OS) following TACE: Patients with elevated MIF concentrations showed a significantly reduced median OS of only 719 days compared to patients below the cut-off value (median OS: 1430 days, p = 0.021).Baseline MIF serum concentrations are associated with tumor size of intrahepatic malignancies and predict outcome of liver cancer patients receiving TACE.

Macrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma

“…Our data are of clinical relevance, as we provide insights into how MIF and its cognate receptor CD74 drive hepatocarcinogenesis in vivo and complement the human studies that have previously indicated a prognostic relevance of MIF and CD74 expression in HCC patients (Hira et al, 2005;Wirtz et al, 2021). Nevertheless, further animal studies are needed to evaluate the effects of an anti-CD74 directed therapy during HCC growth, for example, in models of orthotopic HCC transplant in murine livers previously treated with fibrogenic agents (Liu et al, 2020;Reiberger et al, 2015).…”

Immunoglobulin-like transcript 2 as an impaired anti-tumor cytotoxicity marker of natural killer cells in patients with hepatocellular carcinoma

“…In other studies related to HCC, the expression of MIF was higher in HCC tissues than in healthy or adjacent non-tumor liver tissues ( 17 , 22 ). MIF was measurable in sera from patients with HCC, and the level was associated with hepatic tumor size and outcome of patients receiving transcatheter arterial chemo embolization ( 23 ). One of the limitations of the present study is the lack of analysis between serum MIF levels and expression levels of ILT2 on CD56 dim NK cells due to the scarcity of serum samples.…”

Activity-Based Imaging of Macrophage Migration Inhibitory Factor with a Two-Photon Fluorescent Probe

“…19 In addition, MIF was found to synergistically induce the growth of HCC cells in the research of HCC, 20 which makes it possible to inhibit the growth of HCC by regulating the expression and function of MIF. Given that MIF is an indicator of early diagnosis, a potential therapeutic target, and a biomarker for HCC progression and patient prognosis, 21,22 reliably mapping the levels of MIF is thus greatly important.…”