分泌性白细胞蛋白酶抑制剂在结肠癌中的作用

摘要

目的 观察分泌性白细胞蛋白酶抑制剂(SLPI)在结肠癌发生发展中的作用.方法 免疫组织化学法检测165例结肠癌标本中SLPI的表达,并对SLPI表达与结肠癌临床病理特征的关系进行统计学分析;采用RNA干扰和质粒过表达的方式,改变结肠癌细胞中SLPI的表达水平,观察SLPI表达对结肠癌细胞侵袭能力的影响.结果 SLPI在正常结肠组织中呈阴性表达,在结肠癌组织中呈阳性表达;SLPI的表达水平与与患者性别(P＞0.05)、年龄(P＞0.05)无明显相关,而与肿瘤的分化程度(P＜0.05)、TNM分期(P＜0.05)、淋巴转移(P＜0.01)、远处转移(P＜0.05)明显相关.Cox比例风险回归模型分析显示SLPI表达[风险比(HR)=6.583,95％可信区间(CI):2.247 ～11.985,P＜0.05]是结肠癌患者生存的独立影响因素;Kaplan-Meier法生存分析表明,与SLPI低表达的患者比较,SLPI高表达的结肠癌患者中位生存时间明显缩短(46个月比54个月,P＜0.01).细胞学实验显示,SLPI特异的小干扰RNA (siRNA)能够抑制结肠癌细胞侵袭能力,而过表达SLPI能够促进结肠癌细胞的侵袭能力,基质金属蛋白酶(MMPs)抑制剂XG076能够抑制过表达SLPI促进的结肠癌细胞侵袭过程.结论 SLPI参与结肠癌的发生发展过程,是结肠癌患者预后的独立影响因素.%Objective To investigate the role of secretory leukocyte protease inhibitor (SLPI) expression in the tumorigenesis of colon cancer.Methods Expression of SLPI in colon cancer tissues and normal colon tissues were detected by immunohistochemistry;and its relation with other clinicopathological characteristics was also statistically analyzed.SLPI expression level were decreased or increased by transfection of small interfering RNA (siRNA) or SLPI plasmid in colon cancer cell lines to see how SLPI expression level influenced invasion of colon cancer cells.Results SLPI was negatively expressed in normal colon tissues,while positive expressed in colon cancer tissues.SLPI expression level did not correlated with gender (P ＞ 0.05) and age (P ＞ 0.05),but statistically significantly correlated with tumor differentiation (P ＜ 0.05),TNM stages (P ＜ 0.05),lymph nodal metastasis (P ＜ 0.01) and distant metastasis (P ＜ 0.05).Cox analysis indicated that SLPI expression was independent prognostic factors of colon cancer patients [hazard ratio (HR):6.583,95％ confidence interval (CI):2.247-11.985,P ＜ 0.05].Kaplan-Meier survival analysis showed that,compared with patients with low SLPI expression,patients with high SLPI expression had shortened median survival time (46 months vs.54 months;P ＜ 0.01).Cellular experiments indicated that downregulation or upregulation of SLPI in colon cancer cell lines by transfection of siRNA or SLPI plasmid would decease or increase the invasion of colon cancer.Matrix metalloproteinase inhibitor could inhibited the enhanced invasion of colon cancer cells caused by SLPI overexpression.Conclusion SLPI is involved in the tumorigenesis of colon cancer and is an independent prognostic factor independently influencing the survival of colon cancer patients.