Objective To investigate the diagnostic value of macrophage migration inhibitory factor (MIF) for hepatocellular carcinoma (HCC).MethodsThe research was divided into 2 parts,including testing research and confirmatory research.The clinical data of 269 patients with HCC ( group A) and 390 individuals (including 135 patients with hepatic cirrhosis,106 with benign hepatic diseases and 149 healthy individuals,control group A) who were admitted to the Zhongshan Hospital of Fudan University from January to May,2004,and 173 patients with hepatic cancer (group B) and 257 individuals (including 86 patients with hepatic cirrhosis,79 with benign hepatic diseases and 92 healthy individuals,control group B ) who were admitted from August to December,2004,and 80 patients with HCC who received radical hepatic resection in January 2005 were retrospectively analyzed.Samples of plasma of patients in the group A and individuals in the control group A were collected before operation.Samples of plasma of patients received radical hepatic resection were collected preoperatively and at postoperative day 3,7 and 30.HCC and adjacent issues of patients in the group A were collected.The levels of MIF in the plasma and tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry,respectively.Non-normal distribution data were described as M( QR).Differences between the groups were analyzed by using the Mann-Whitney U test,and the relationship between the levels of MIF in the plasma and tissues was detected by the Spearman correlation coefficient.The diagnostic value of MIF was analyzed by the ROC curve.ResultsThe levels of MIF in the plasma of patients in the group A and individuals in the control group A were 85.7 μg/L (58.8 μg/L) and 15.5 μg/L(31.6 μg/L),respectively.The levels of MIF in the plasma of the patients with hepatic cirrhosis,benign hepatic diseases and healthy individuals were 24.9 μg/L (12.6 μg/L),12.5 μg/L(7.3 μg/L) and 13.2 μg/L (7.7 μg/L),respectively.There was a significant difference in the level of MIF between the group A and the control group A (F =54.235,P ＜ 0.05 ).The area under the ROC curve reached peak when the level of MIF in the plasma was 35.3μg/L.Compared with the control group B,the vdues of AUC,sensitivity and specificity were 92.1％,90.7％ and 93.4％ in the group B.The levels of MIF of the patients with HCC before operation and at 3,7,and 30 days after operation were 81.0 μg/L(54.0 μg/L),76.1 μg/L(47.5 μg/L),50.9 μg/L (40.7 μg/L) and 18.7 μg/L ( 15.1 μg/L),respectively.The levels of MIF decreased with time passed by,and were back to normal at 30 days after the operation.The median expressions of MIF in the HCC and adjacent issues were 0.083 and 0.007,respectively,with a significant difference ( U =3.975,P ＜ 0.05).The expression of MIF in the plasma was positively correlated with its expression in the HCC tissue ( r =0.759,P ＜ 0.05 ).ConclusionMIF plays an important role in the genesis and development of HCC and has potential to be one of the molecular markers for the diagnosis of HCC.

Objective By analyzing the expression of cluster of differentiation 74 (CD74) in hepatocellular carcinoma (HCC) and HCC cell lines,the correlation between the level of CD74 expression and the patients' prognosis was investigated.MethodsThe expression of CD74 in high metastatic potential HCC cell lines(MHCC-LM3,MHCC-97H),low metastatic potential HCC cell line( MHCC-97L),and no metastatic potential HCC cell line(Hep-G2) were estimated by Western blot.The paraffin embedded tissues which include intra-tumor and paratumor tissues were collected from 320 patients who had received HCC curative surgical resection and 5 normal liver tissues from the donors of liver tranplantation.The high density tissue micro-array was made of these specimens. Immunol-histochemistry was applied to discover the different levels of CD74 in tumor,paratumor and normal liver tissues.Survival curves were generated by the Kaplan-Meier method and verified by the Logrank test.Cox proportional hazards regression analysis was applied to estimate the prognostic factors in multivariate analysis.ResultsThe expression level of CD74 was significantly higher in low metastatic potential and no metastatic potential HCC cell lines (MHCC-97L 1.224 ±0.014,Hep-G2 1.374 ±0.006) than that in high metastatic potential ones( MHCC-LM3 0.622 ±0.078,MHCC-97H 0.732 ± 0.083 ).Significant differences can be found between the groups (t =- 13.308,- 16.849,- 10.177,- 13.436,- 17.057; P ＜0.01 ).Meanwhile,in tumor tissues,the CD74 was expressed positively in 221 patients and negatively in 99 patients.But CD74 was expressed slightly in paratumor and negatively in 5 normal liver tissues.There's no significant differences between the groups categorization according to age,HBsAg,cirrhosis,AFP level,tumor number,tumor size,tumor capsule,blood vessel invasion,Edmondson Grades and tumor nodes metastasis classification (TNM) stages (x2 =0.053,0.141,1.200,0.000,0.277,1.975,0.263,1.044,0.000,0.433 ; P ＞ 0.05 ),except gender (x2 =3.954,P ＜ 0.05).Kaplan-Meier method showed that patients with positively expression of CD74 had better prognosis than others (x2 =5.620,P ＜ 0.05 ).Cox proportional hazards regression analysis showed that CD74 was a significant and independent prognostic factor of survival [ hazard ratio (HR) =0.721,95％confidence interval (CI) =0.522 - 0.996,P ＜ 0.05 ].Conclusion The expression of CD74 in hepatocellular carcinoma could be a biomarker of the prognosis and there's some potential correlation with cancer cell apoptosis.