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目的:分析肝细胞癌患者术前血浆中巨噬细胞移动抑制因子(macrophage migration inhibitory factor,MIF)浓度,及其与临床病理特征和预后的关系。方法:用双抗夹心酶联免疫吸附实验(ELISA)测定44例肝细胞癌和20例肝良性占位患者血浆中MIF、血管内皮生长因子(vascular endothelial growth factor,VEGF)、IL-8浓度,分析血浆MIF浓度与临床病理特征和预后的关系。结果:肝癌患者血浆MIF浓度高于肝良性占位患者,差异有统计学意义(中位浓度,9.09ng.mL-1对4.80ng.mL-1;P=0.002)。肝癌患者血浆MIF与VEGF浓度呈正相关(r=0.547,P<0.001)。血浆MIF浓度和肿瘤数目(P<0.001)、大小(P=0.039)、包膜完整性(P=0.044)、血管侵犯(P=0.041)、临床TNM分期(P<0.001)有关。低MIF表达(<9.09ng.mL-1)患者的总体生存时间(中位总体生存时间,26.9个月对20.3个月;P=0.0069)和无瘤生存时间(中位生存时间,24.5个月对12.3个月;P=0.0023)明显高于高MIF表达(>9.09ng.mL-1)患者。多因素分析结果表明,血浆MIF水平是影响肝癌患者术后总体生存和无瘤生存的独立危险因素。结论:MIF可能通过刺激VEGF分泌影响肿瘤血管生成,进而促进肿瘤的转移复发。血浆MIF可能成为肝癌侵袭性的生物学标志和预测患者预后的独立指标。
Objective: To analyze the plasma concentration of macrophage migration inhibitory factor (MIF) in patients with hepatocellular carcinoma and its relationship with clinicopathological features and prognosis. Methods: The plasma concentrations of MIF, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in 44 hepatocellular carcinoma and 20 benign liver lesions were determined by enzyme-linked immunosorbent assay (ELISA) The relationship between plasma MIF concentration and clinicopathological features and prognosis was analyzed. Results: The plasma MIF levels in patients with HCC were significantly higher than those in benign liver patients (median, 9.09ng.mL-1 vs. 4.80ng.mL-1; P = 0.002). There was a positive correlation between plasma MIF and VEGF concentration in patients with liver cancer (r = 0.547, P <0.001). Plasma MIF levels correlated with the number of tumors (P <0.001), size (P = 0.039), envelope integrity (P = 0.044), vascular invasion (P = 0.041) and clinical TNM stage (P <0.001). Overall survival (median overall survival, 26.9 months versus 20.3 months; P = 0.0069) and disease-free survival (median survival time, 24.5 months) in patients with low MIF expression (<9.09 ng.mL- Vs. 12.3 months; P = 0.0023) was significantly higher in patients with high MIF expression (> 9.09 ng.mL-1). Multivariate analysis showed that plasma MIF level was an independent risk factor for overall survival and tumor-free survival in patients with liver cancer. Conclusion: MIF may affect tumor angiogenesis by stimulating the secretion of VEGF, thereby promoting tumor metastasis and recurrence. Plasma MIF may become a biomarker of invasiveness of hepatocellular carcinoma and an independent predictor of prognosis in patients.