肝癌患者血浆巨噬细胞移动抑制因子水平及其临床意义

Plasma Level of Macrophage Migration Inhibitory Factor(MIF) Plays a Role in Prognosis of the Patients with Hepatocellular Carcinoma After Curative Resection

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：We measured the plasma levels of macvophage migration in hibitory factor（MIF） in patients with HCC befvre curative resection to investigate its relationship with clinicopathological features and prognosis.Methods：ELISA was used to detect the concentrations of MIF,vascular endothelial growth factor（VEGF） in preoperative plasma of 44 patients with curative resection of HCC and 20 negative subjects.The plasma MIF levels were compared between different groups divided by clinicopathological features.The prognosis value was evaluated by survival analysis and Cox regression.Results：The plasma level of MIF was significantly higher in patients with HCC compared with negative subjects（median,9.09 ng·mL^-1 vs.4.80 ng·mL^-1,P=0.002）.In HCC plasma samples,there was a significantly correlation between plasma MIF and VEGF concentration（r=0.547,P〈0.001）.The level of MIF correlated significantly with multiple tumor（P〈0.001）,larger tumor size（P=0.039）,absence of tumor capsule（P=0.044）,presence of venous invasion（P=0.041） and advanced pathological stage（P〈0.001）.By Kaplan-Meier analysis,we found that patients with high MIF level（〉9.09 ng·mL^-1） had a poorer overall survival（median overall survival,20.3 months vs.26.9 months,P=0.0069） and disease-free survival（median disease-free survival,12.3 months versus 24.5 months,P=0.0023） than those with low MIF level（〈9.09ng·mL^-1）.Multivariate analyses showed that plasma MIF was a significantly and independent prognostic factor of survival.Conclusion：MIF may be potential to promote metastasis of HCC by stimulating angiogenic factors.MIF level in plasma may be a useful biological marker of carcinoma invasiveness and independent factor for predicting the prognosis.