巨噬细胞迁移抑制因子在胆囊癌组织中的表达水平与临床病理特征和预后的关系

The relationship between the expression of macrophage migration inhibitory factor in gallbladder tissues and clinicopathological features and prognosis

目的探讨巨噬细胞迁移抑制因子(MIF)在胆囊癌组织中的表达水平与临床病理特征和预后的关系,及其对胆囊癌细胞迁移、侵袭能力的影响。方法选取复旦大学附属中山医院胆囊癌组织78例,炎症组织17例,采用免疫组织化学法研究MIF蛋白的表达水平,分析其与年龄、性别、肿瘤病理分期、TMN分期、淋巴结转移、远处转移等临床病理因素的关系及生存情况,并采取Cox多因素回归模型预测影响胆囊癌患者预后的危险因素。通过质粒过表达胆囊癌细胞株(GBC-SD、NOZ)中的MIF蛋白,采用Transwell法比较肿瘤细胞迁移、侵袭能力的差异。结果MIF在胆囊癌组织中的表达高于炎症组织(4.45±3.74比2.14±2.05,P<0.05),且MIF的表达与肿瘤的T分期(P<0.05)、TNM分期(P<0.05)显著相关。MIF免疫反应阳性的患者中位生存时间低于MIF免疫反应阴性的患者(9例比13例,P<0.05)。MIF表达是影响胆囊癌患者预后的独立因素(P<0.05)。过表达MIF后,胆囊癌细胞GBC-SD、NOZ的迁移能力增强[(125.00±11.36)个比(62.67±17.16)个,P<0.05;(145.00±17.58)个比(78.00±13.75)个,P<0.05],侵袭能力也明显增强[(116.00±5.69)个比(68.00±10.82)个,P<0.05;(156.00±12.29)个比(82.00±8.54)个,P<0.05]。结论MIF在胆囊癌组织中高表达,与胆囊癌患者的不良预后有关,MIF具有促进胆囊癌细胞迁移和侵袭的能力。

Objective To investigate the relationship between the expression of macrophage migration inhibitory factor (MIF) in the gallbladder tumor tissues and clinicopathological features and prognosis, as well as the impact on the migration, invasion of gallbladder cancer cells. Methods Immunohistochemical method was performed to detect expression of MIF in tissue microarray of gallbladder, including seventy-eight tumor tissues and seventeen inflammation tissues from Zhongshan Hospital Affiliated Fudan University. The connection between the expression of MIF and clinicopathologic factors was analyzed, such as age, gender, pathological staging, TNM staging, lymphatic metastasis, distant metastasis. The overall survival between MIF positive-expression and MIF negative-expression were compared. Cox multiple regression model was introduced to indicate essential prognostic factor for gallbladder cancer. Then, the migration and invasion of gallbladder cancer cells (GBC-SD, NOZ) were analyzed by Transwell method using plasmid-induced overexpression of MIF. Results The expression of MIF in gallbladder tumor tissues was higher than that in inflammation tissue (4.45±3.74 vs. 2.14±2.05, P<0.05) and it was significantly correlated with T staging (P<0.05)and TNM staging (P<0.05). Furthermore, patients with positive-expression of MIF had a shorter median survival time (9 vs. 13, P<0.05). MIF could be an independent prognostic factor for gallbladder cancer (P<0.05). Migration and invasion in GBC-SD and NOZ were increased [(125.00±11.36) cells vs.(62.67±17.16) cells, P<0.05;(145.00±17.58) cells vs.(78.00±13.75) cells, P<0.05),(116.00±5.69) cells vs.(68.00±10.82) cells, P<0.05;(156.00±12.29) cells vs.(82.00±8.54) cells, P<0.05]. Conclusion MIF is overexpressed in gallbladder tumor tissues with a negative influence on prognosis, and can promote the migration and invasion in gallbladder cancer cells.