title: Validity of plasma macrophage migration inhibitory factor for diagnosis and prognosis of hepatocellular carcinoma.
abstract: We performed our study to determine whether plasma macrophage migration inhibitory factor (MIF) levels have diagnostic and prognostic value in hepatocellular carcinoma (HCC) patients. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to measure the expression of MIF in plasma and tissues, respectively. Plasma MIF levels were compared to HCC occurrence, clinicopathological features and outcomes. Cutpoints of plasma MIF levels for diagnosis and prognosis were, respectively, determined by receiver operating characteristic analysis and X-tile in corresponding training cohort, and then were confirmed in the validation cohort. The postoperative plasma MIF levels of HCC patients were detected in an independent cohort (80 HCC patients). As a result, MIF expression in situ was mainly observed in the cytoplasm of HCC cells. Intratumoral MIF expression was positively correlated with plasma MIF levels (r = 0.759, p < 0.001). Compared to serum α-fetoprotein (AFP), plasma MIF had a higher diagnostic value for discrimination of HCC from controls at 35.3 ng/ml. With determined cutpoints, plasma MIF levels demonstrated a significant association with overall survival (OS) and disease-free survival (DFS) of HCC patients even in patients with normal serum AFP levels and Tumor Node Metastasis (TNM) stage I. In addition, the plasma MIF levels were identified as an independent factor for OS [hazard ratio (HR) = 1.754; p = 0.012] and DFS (HR = 2.121; p < 0.001). Plasma MIF levels decreased markedly within 30 days after tumor resection (p < 0.001). Therefore, plasma MIF levels have potential as a diagnostic and prognostic factor for HCC.
authors.affiliation: Liver Cancer Institute, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhao
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Hei
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiu-Tao
authors.initials: XT
authors.lastname: Fu
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Wang
authors.forename: Shun-Cai
authors.initials: SC
authors.lastname: Zhang
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D008263:Macrophage Migration-Inhibitory Factors