TABLE 5.
Patient studies of MIF in pancreatic cancer.
| Sampling type | Key findings | Refs |
|---|---|---|
| Plasma. PC patients (n = 30), healthy controls (n = 10) | Plasma MIF levels in PC (mean 36 ng/ml) was significantly higher than healthy controls (24 ng/ml) (p = 0.038) | Winner et al. (2007) |
| Plasma. PC patients (n = 18), healthy controls (n = 19) | Plasma MIF levels in PC were not significantly different from healthy controls with an average increase of 30% (p = 0.15) | Fredriksson et al. (2008) |
| Plasma. PDAC patients (n = 78) | 1) mean plasma MIF levels in PDAC patients was 7,240 pg/ml; 2) plasma PTX3 levels were positively correlated with levels of MIF (r = 0.38, p = 0.001) | Kondo et al. (2013) |
| Serum. PC (n = 17), AP (n = 26), CP (n = 26), healthy controls (n = 16) | 1) compared with healthy controls, serum MIF levels in PC patients and pancreatitis patients were 10.6-fold and 9.2-fold higher, respectively; 2) the AUC of serum MIF in discriminating PC patients from healthy controls or all controls (including AP, CP, and healthy controls) were 1.00 or 0.78, respectively | Chen et al. (2010) |
| Pancreatic tissue. DM-PC, CP, and healthy controls. Serum. PC and non-PC patients: New-onset DM-PC (n = 35), PC without DM (n = 35), new-onset T2DM (n = 35), healthy controls (n = 35) | 1) MIF expression was significantly higher in DM-PC tissues than CP or PC patients without DM; 2) mean serum MIF levels (ng/ml) were higher in new-onset DM-PC (32), vs. PC without DM (17, p < 0.001), long-term DM-PC (20, p < 0.001), new-onset T2DM patients (21, p < 0.01), and healthy controls (14, p < 0.001); 3) diagnostic utility of serum MIF in distinguishing new-onset DM-PC from new-onset T2DM: AUC, 0.85; Se, 86%; Sp, 60% | Tan et al. (2014) |
| Pancreatic tissue. PDAC patients (n = 11), healthy controls (n = 7) | 1) MIF protein expression in PC nests was 2.7-fold higher than normal pancreatic ducts; 2) the AUC of pancreatic MIF levels in discriminating PC from normal pancreas was >0.7 with p < 0.001 | Cui et al. (2009) |
| Pancreatic tissue. PDAC patients (n = 11), CP (n = 9), Paired tissue. PDAC patients (n = 11), healthy controls (unknown) | MIF mRNA expression in pancreatic tissues was higher in PDAC than CP, stromal tissue of PDAC, and normal ductal area | Denz et al. (2010) |
| Pancreatic tissue. PDAC patients (n = 57) | 1) higher MIF expression in tumors was associated with poorer survival independent of tumor stage; 2) IHC showed an increased expression of MIF in cancer cells compared with surrounding non-tumor ductal cells | Funamizu et al. (2013) |
| Pancreatic tissue. PDAC patients (n = 64) | DDT was over-expressed in PDAC tissues in a pattern positively correlated with that of MIF (r = 0.346, p = 0.0001) | Guo et al. (2016) |
| Plasma and pancreatic tissue. PanIN and PDAC patients (n = 40), healthy donors (n = 91) | 1) plasma levels of both total MIF and oxMIF were not significantly different between PC patients and healthy donors; 2) in IHC, oxMIF was over-expressed in PanINs and PDAC tissues and was correlated with cancer stage, stronger in later stage tumors; adjacent normal pancreatic tissue did not show oxMIF staining | Schinagl et al. (2016) |
| Pancreatic tissue. PDAC patients: MIF-high (n = 43), MIF-low (n = 42) | 1) the majority of PDAC tumor tissue (75/85) exhibited significantly higher MIF expression than paired noncancerous tissue; 2) higher MIF expression in tumor tissue is associated with poor survival of PDAC patients (p = 0.023) | Wang et al. (2018) |
| Pancreatic tissue. PDAC patients: 1) test cohort (n = 69): MIF-high (n = 35), MIF-low (n = 34); 2) validation cohort-1 (n = 41): MIF-high (n = 21), MIF-low (n = 20); 3) validation cohort-2 (n = 69): MIF-high (n = 35), MIF-low (n = 34) | 1) miRNA profiling identified 53 differentially expressed miRNAs in MIF-high vs. MIF-low tumors, a higher expression of miR-301b, miR-15b, miR-10b, miR-93, and miR-590–5p in MIF-high tumors were also associated with poor survival in PDAC cases; 2) MIF expression in the tumor was positively correlated with miR-301b and negatively correlated with NR3C2 expression | Yang et al. (2016) |
| Exosomes isolated from plasma. PDAC patients: With liver metastasis (n = 18), with no evidence of disease five years post-diagnosis (n = 10), with progression of disease post-diagnosis (n = 12), healthy controls (n = 15) | 1) MIF levels in exosomes isolated from PDAC with progression of disease post-diagnosis were significantly higher than PDAC with no evidence of disease 5 years post diagnosis and healthy controls; 2) MIF levels were lower in PDAC patients with liver metastasis that those with progression of disease, without significance | Costa-Silva et al. (2015) |
MIF, macrophage migration inhibitory factor; PC, pancreatic cancer; PDAC, pancreatic ductal adenocarcinoma; AUC, area under the receiver operating characteristic curve; AP, acute pancreatitis; CP, chronic pancreatitis; IHC, immunohistochemistry; PTX3, pentraxin3; DM-PC, pancreatic cancer associated diabetes mellitus; T2DM, type-2 diabetes mellitus; Se, sensitivity; Sp, specificity. PanIN, pancreatic intraepithelial neoplasia; DDT, D-dopachrome tautomerase; oxMIF, oxidative MIF.