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MIF mRNA and protein expression in five lung squamous cell carcinoma cell lines. MIF mRNA and protein were detected in all cell lines with higher expression in HCC‐1588 compared with those of others.
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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...
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Objective:
Endothelial cell-specific molecule 1 (ESM1) has been implicated as an oncogene in several types of cancer. However, the potential role of ESM1 in esophageal carcinogenesis (ESCA)/esophageal squamous cell carcinoma (ESCC) is still unclear.
Methods:
The expression, function, and survival data of ESM1 were observed using a bioinformatics...
Citations
... Specifically, the cutoff point values for defining high and low expression of MIF, CTNNB1, and CDH1 were as follows: <14. 33 ...
... In patients with high-grade osteosarcoma, Han et al found that MIF overexpression was associated with poor OS and metastasis-free survival [32]. In two other studies on patients with esophageal squamous cell carcinoma and lung squamous cell carcinoma, high MIF levels compared to low MIF levels were associated with worse OS or diseasespecific survival and disease-free survival, respectively [23,33], supporting our study results. Some studies in pancreatic ductal adenocarcinoma and gastric cancer showed that elevated expression of MIF corresponded with unfavorable OS [34,35]. ...
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 MIF ⁿ and MIF m‐c levels compared to those with low MIF ⁿ and MIF m‐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.
... Kamimura et al. showed that the intracellular distribution of MIF predicted prognosis of patients with lung adenocarcinomas [32]. In another study with 96 patients with squamous cell carcinomas of the lung, high MIF levels were associated with lymph node metastases, shorter disease-free survival and shorter diseasespecific survival [33]. Altogether, MIF may not only provide additional insight into the linkage between inflammation and tumor growth, but also has the potential to function as a novel biomarker in lung cancer. ...
... According to the results shown in Table 3, no significant differences were found. As MIF expression levels in tissue samples of squamous cell carcinomas (SCC) have been found to be associated with tumor progression [33], further analyses of MIF in patients with SCC were performed. No differences in MIF concentrations between responders and non-responders to chemotherapy within the SCC cohort were observed in pretherapeutic samples (p = 0.919), at cycle 2 (p = 1.000) or at cycle 3 (p = 0.546). ...
... It has already been shown that MIF may facilitate prognosis in lung cancer [32,33]. In the present study, we investigated the possible use of MIF and proGRP for prediction of therapy response and stratification of overall survival in a cohort of lung cancer patients. ...
Background:
Lung cancer is a major burden to global health and is still among the most frequent and most lethal malignant diseases. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in a variety of processes including tumorigenesis, formation of a tumor microenvironment and metastasis. It is therefore a potential prognostic biomarker in malignant diseases.
Objective:
In this study, we investigated the applicability of MIF in serum samples as a biomarker in lung cancer.
Methods:
In a retrospective approach, we analyzed the sera of 79 patients with non-small-cell lung cancer (NSCLC) and 14 patients with small-cell lung cancer (SCLC) before the start of chemotherapy, as well as before the second and third chemotherapy cycle, respectively. Serum MIF levels were measured using a sandwich immunoassay with a sulfo-tag-labelled detection antibody, while pro-gastrin releasing peptide (proGRP) levels were determined with an enzyme-linked immunosorbent assay.
Results:
No difference in serum MIF levels between responders and non-responders to chemotherapy was observed at all time points, while proGRP levels were significantly lower in responders before the second chemotherapy cycle (p = 0.012). No differences in biomarker levels depending on the histopathological classification of NSCLC patients was found. Moreover, in ROC curve analyses MIF was not able to distinguish between responders and non-responders to therapy. proGRP could differentiate between responders and non-responders before the second chemotherapy cycle (p = 0.015) with sensitivities of 43% at 90% and 95% specificity, respectively. Likewise, proGRP yielded significantly longer survival times of patients with low proGRP concentrations before the second chemotherapy cycle (p = 0.015) in Kaplan-Meier analyses, yet MIF showed no significant differences in survival times at all time points. Comparison with the biomarkers CEA and CYFRA 21-1 in the same cohort showed that these established biomarkers clearly performed superior to MIF and proGRP.
Conclusions:
From the present results, there is no indication that serum MIF may serve as a biomarker in prognosis and monitoring of response to therapy in lung cancer. Limitations of this study include its retrospective design, the inclusion of a larger NSCLC and a smaller SCLC subgroup, the classical chemotherapeutic treatment, the use of a non-diagnostic immunoassay (RUO-test) for MIF measurement and the lack of a validation cohort. Strengths of the study are its highly standardized procedures concerning sample collection, preanalytic treatment, measurements and quality control of the laboratory assays.
... These findings may be a clear example that MIF could exhibit a different behavior depending on the mechanisms that have triggered it and that it could have a protective function in acute inflammation but can contribute to carcinogenesis in chronic inflammation as described in SCC. Despite some authors have suggested that MIF may be used as a serological biomarker in some types of non-cutaneous SCC (Zepeda-Nuño et al., 2021) or prognostic marker in SCC of the lung (Koh et al., 2019), we did not evaluate the expression of MIF mRNA, nor the expression of MIF in tumoral tissue. These limitations of the work should be taken into account for further work if trying to assess MIF as a biomarker in cutaneous SCC. ...
Background:
Some cytokines are strongly implicated in the development of squamous cell carcinoma (SCC) such as the Macrophage migration inhibitory factor (MIF). The haplotype -794 (CATT)5-8 /-173G>C in MIF gene polymorphisms has been associated with some types of cancer. The aim of this study is to establish the possible association between the presence of this haplotype in the MIF gene and its subsequent soluble levels with the susceptibility of SCC in western Mexican population.
Methods:
This study included 175 SCC patients and 175 age-sex-matched individuals as a reference group (RG) from western Mexico. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms were genotyped by endpoint PCR and PCR-RFLP, and the determination of MIF serum levels was measured by ELISA. Clinical characteristics were evaluated by a group of dermatologists.
Results:
Analysis of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms showed that the 5C (OR = 2.7, p = 0.02) and the 7G (OR = 3.39, p < 0.01) haplotypes are associated with susceptibility in SCC. MIF soluble levels in SCC patients showed a median of 13.93 ng/mL, whereas the reference group showed 6.000 ng/mL.
Conclusions:
Our findings suggest that 5C and 7G [-794(CATT)5-8 /-173G>C] MIF gene haplotypes are associated with susceptibility to SCC and that SCC patients present increased soluble levels of MIF.
... To date, there have been many studies regarding the prognostic role of RAB27A and RAB27B expression through immunohistochemical staining methods in various cancer types (12)(13)(14)(15)(16)(17)(18). In clear cell renal cell carcinoma renal cell carcinoma, we confirmed that RAB27A expression was strongly positive in a large group of patients. ...
Background/aim:
RAB27A and RAB27B are involved in exosome secretion. To date, there have been many attempts to elucidate the roles of RAB27A and RAB27B in the prognosis of various cancer types. The association of RAB27A and RAB27B expression with the clinical and pathological features was evaluated in patients with stomach cancer.
Materials and methods:
A total of 360 patients who had undergone surgery for stomach cancer between January 1999 and December 2007 at Gyeongsang National University were enrolled in the study. Disease-free survival (DFS) and disease-specific survival (DSS) were compared according to immunohistochemistry of tumor samples. RAB27A and RAB27B mRNA and protein were also extracted from four stomach cancer cell lines using quantitative polymerase chain reaction and western blotting.
Results:
Strong nuclear RAB27A expression in tumor samples was statistically significantly correlated with lymph node metastasis. Cytoplasmic RAB27B expression was related to poor disease-free survival and its combined cytoplasmic and membranous expression was related to disease-specific survival of patients with different histopathological types of stomach cancer. High RAB27A expression and high RAB27B expression was found in four stomach cancer cell blocks. Among the four cell lines, NCI-N87 exhibited the lowest relative mRNA density and HS746T exhibited the highest relative protein density for both RAB27A and RAB27B.
Conclusion:
RAB27A and RAB27B expression may help predict lymph node metastasis and survival of patients with gastric cancer.
... [3][4][5][6][18][19][20][21][22] MIF is overexpressed in many solid tumors, including prostate, [23] hepatocellular, [24] gastric, [25] and adenocarcinoma and squamous cell carcinoma of the lung. [26,27] In most of tumors, the degree of MIF overexpression is positively correlated with tumor progression or metastatic potential. [8] It has been shown that neutralizing anti-MIF antibodies inhibit tumor angiogenesis in murine malignant lymphoma, [18] murine colon cancer, [19] and a human melanoma model. ...
Macrophage migration inhibitory factor (MIF) is a cytokine that mediates the interaction between malignant cells and the innate immune system. Recently, MIF has received attention for its role in tumorigenesis. We evaluated the prognostic role of MIF in clear cell renal cell carcinoma (CCRCC).
A total of 152 patients, who underwent nephrectomy for CCRCC were enrolled in this study. Immunohistochemical staining of tissue microarray blocks containing 298 cores—2 cores per CCRCC patient was performed. The relationship between MIF expression and clinicopathological factors was evaluated. Total RNA and protein were extracted from 7 RCC (renal cell carcinoma) cell lines. MIF was knocked down in Caki-2 cells, and a wound healing assay was performed to evaluate migratory activity.
Among the 298 cores, 180 (60.4%) were positive for MIF. Multivariate analysis, showed that, CCRCC patients with negative MIF expression exhibited poor disease-free survival (hazard ratio: 2.087, 95% confidence interval: 0.821–5.307, P value: .023) and poor disease-specific survival (hazard ratio: 2.101, 95% confidence interval: 1.009–4.374, P value: .047). The wound healing assay revealed that cell confluence was lower in MIF-deficient Caki-2 cells than in control cells.
Negative MIF expression might be an independent prognostic marker for patients with CCRCC.
... [3,5,6] Moreover, the overexpression of MIF has been associated to tumor progression, metastasis and unfavorable prognosis in gastric, hepatocellular, pancreatic, and lung cancers, and oral squamous cell carcinoma and metastatic melanoma. [3,7,8] However, the association between MIF expression and survival in patients with cancer is not systematically understood. In this study, we performed meta-analysis to comprehensively assess the prognostic significance of MIF expression in cancer patients. ...
... [10] Furthermore, MIF has been suggested as a potential prognostic factor for various cancers including gastric, hepatocellular, pancreatic, and lung cancers, and oral squamous cell carcinoma and metastatic melanoma. [3,7,8] Therefore, we conducted this meta-analysis to calculate the prognostic significance of MIF expression in cancer patients. We found 8 eligible studies. ...
... Han et al [11] showed that high expression of MIF was related with poor OS and metastasis-free survival in patients with high-grade osteosarcoma. Zhang et al [12] and Koh et al [8] demonstrated significantly poorer OS or diseasespecific survival and DFS with high expression of MIF compared with low expression in patient with esophageal squamous cell carcinoma and lung squamous cell carcinoma, respectively. Kang et al [13] revealed the relationship between MIF expression and OS and recurrence-free survival in patients with oral squamous cell carcinoma. ...
Background:
Recent studies showed that Macrophage migration inhibitory factor (MIF) is overexpressed and closely associated with prognosis in cancer patients. The present study was systematically evaluated the prognostic significance of MIF expression in cancer patients.
Methods:
PubMed, Cochrane library and Scopus were searched for eligible studies up to January 2020. Pooled hazard ratio with confidence interval (CI) was determined to assess the relationship between MIF expression and survival in cancer patients.
Results:
A total of 8 studies comprising 847 cancer patients were included in this meta-analysis. For overall survival, the pooled hazard ratio was 2.23 (95% CI 1.67-2.99, P < .001). For disease-free survival, the pooled hazard ratio was 2.24 (95% CI 1.69-2.96, P < .001). The results suggested that high expression of MIF was significantly related to poor overall survival and disease-free survival in cancer patients.
Conclusion:
MIF expression could be a valuable prognostic factor in cancer patients.
Discovered as inflammatory cytokines, MIF and DDT exhibit widespread expression and have emerged as critical mediators in the response to infection, inflammation, and more recently, in cancer. In this comprehensive review, we provide details on their structures, binding partners, regulatory mechanisms, and roles in cancer. We also elaborate on their significant impact in driving tumorigenesis across various cancer types, supported by extensive in vitro, in vivo, bioinformatic, and clinical studies. To date, only a limited number of clinical trials have explored MIF as a therapeutic target in cancer patients, and DDT has not been evaluated. The ongoing pursuit of optimal strategies for targeting MIF and DDT highlights their potential as promising antitumor candidates. Dual inhibition of MIF and DDT may allow for the most effective suppression of canonical and non-canonical signaling pathways, warranting further investigations and clinical exploration.
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with a pleiotropic spectrum of biological functions implicated in the pathogenesis of cancer and inflammatory diseases. MIF is constitutively present in several cell types and non-lymphoid tissues and is secreted after acute stress or inflammation. MIF triggers the release of proinflammatory cytokines, overrides the anti-inflammatory effects of glucocorticoids, and exerts chemokine function, resulting in increased migration and recruitment of leukocytes into inflamed tissue. Despite this, MIF is a challenging target for therapeutic intervention because of its ubiquitous nature and presence in the circulation and tissue of healthy individuals. Oxidized MIF (oxMIF) is an immunologically distinct disease-related structural isoform found in the plasma and tissues of patients with inflammatory diseases and in solid tumor tissues. MIF converts to oxMIF in an oxidizing, inflammatory environment. This review discusses the biology and activity of MIF and the potential for autoimmune disease and cancer modification by targeting oxMIF. Anti-oxMIF antibodies reduce cancer cell invasion/migration, angiogenesis, proinflammatory cytokine production, and ERK and AKT activation. Anti-oxMIF antibodies also elicit apoptosis and alter immune cell function and/or migration. When co-administered with a glucocorticoid, anti-oxMIF antibodies produced a synergistic response in inflammatory models. Anti-oxMIF antibodies therefore counterregulate biological activities attributed to MIF. oxMIF expression has been observed in inflammatory diseases (eg, sepsis, psoriasis, asthma, inflammatory bowel disease, and systemic lupus erythematosus) and oxMIF has been detected in ovarian, colorectal, lung, and pancreatic cancers. In contrast to MIF, oxMIF is specifically detected in plasma and/or tissues of diseased patients, but not in healthy individuals. Therefore, as a druggable isoform of MIF, oxMIF represents a potential new therapeutic target in inflammatory diseases and cancer. Fully human, monoclonal anti-oxMIF antibodies have been shown to selectively bind oxMIF in preclinical and phase I studies; however, additional clinical assessments are necessary to validate their use as either a monotherapy or in combination with standard-of-care regimens (ie, immunomodulatory agents/checkpoint inhibitors, anti-angiogenic drugs, chemotherapeutics, and glucocorticoids).
