趋化素样因子超家族6与程序性死亡配体1在胶质瘤中的表达及其临床意义

目的检测趋化素样因子超家族6(CMTM6)及程序性死亡配体1(PD-L1)在胶质瘤组织中的表达,并分析两种蛋白的表达相关性及其对预后的影响。方法收集郑州大学第五附属医院神经外科收治的胶质瘤患者76例与同时期脑外伤开颅患者(对照组)40例,留取术中组织标本,通过免疫组织化学法(IHC)和蛋白质印迹法(Western blot)检测组织样本中CMTM6及PD-L1的表达情况,分别采用χ²检验及独立样本t检验分析表达是否有差异,并对两者表达做相关性分析。对胶质瘤术后患者随访36个月,并做生存分析。结果IHC结果显示CMTM6在胶质瘤组的阳性率明显高于对照组77.6%(59/76)比22.5%(9/40),χ²=32.838,P<0.05],差异有统计学意义,高级别胶质瘤(HGG)的阳性率明显高于低级别胶质瘤(LGG)88.1%(37/42)比64.7%(22/34),χ²=5.919,P<0.05],差异有统计学意义,HGG的高表达率明显高于LGG78.4%(29/37)比40.9%(9/22),χ²=8.449,P<0.05],差异有统计学意义;PD-L1在胶质瘤组的阳性率明显高于对照组51.3%(39/76)比12.5%(5/40),χ²=16.771,P<0.05],差异有统计学意义,HGG的阳性率明显高于LGG61.9%(26/42)比38.2%(13/34),χ²=4.214,P<0.05],差异有统计学意义,HGG的高表达率明显高于LGG50.0%(13/26)比7.7%(1/13),P<0.05],差异有统计学意义;CMTM6与PD-L1表达呈现显著相关性(r=0.535,P<0.05)。蛋白质印迹法(Western blot)结果,CMTM6在胶质瘤中的表达高于对照组(1.04±0.51比0.32±0.06,t=12.174,P<0.05),差异有统计学意义,在HGG中的表达高于LGG(1.26±0.46比0.78±0.44,t=4.641,P<0.05),差异有统计学意义,PD-L1在胶质瘤中的表达高于对照组(0.68±0.57比0.21±0.11,t=6.896,P<0.05),差异有统计学意义,在HGG中的表达高于LGG(0.92±0.61比0.38±0.32,t=4.963,P<0.05),差异有统计学意义。Kaplan-Meier生存分析显示,CMTM6/PD-L1表达阳性者预后比阴性者差(χCMTM62=5.371,χPD-L12=9.570,P<0.05),高表达者预后比低表达者差(χCMTM62=7.282,χPD-L12=6.777,P<0.05)。结论CMTM6/PD-L1在胶质瘤组织中明显表达上调,且两者呈正相关,表达强度与胶质瘤的病理级别紧密相关,表达水平与生存时间呈负相关。

Expression of chemokine-like factor superfamily 6 and programmed death ligand 1 in glioma and its clinical significance

Objective To detect the expression of chemokine-like factor superfamily 6(CMTM6)and programmed death ligand 1(PD-L1)in glioma tissues,and to analyze the correlation between the expression of the two proteins and their influence on prognosis.Methods Intraoperative tissue specimens were collected from 76 patients with glioma and 40 patients with brain trauma at the same time(control group)admitted to the Neurosurgery Department of our hospital.The expression of CMTM6 and PD-L1 in the tissue samples was observed by immunohistochemistry(IHC)and Western blotting.Chi-square and independent sample t-tests were used respectively to analyze the differences of expression,and the correlation was analyzed.The patients with glioma were followed up for 36 months,and the survival analysis was performed.Results IHC results showed that the positive rate of CMTM6 in glioma group was significantly higher than that in control group77.6%(59/76)to 22.5%(9/40),χ²=32.838,P<0.05].The positive rate of high-grade glioma(HGG)was significantly higher than that of low-grade glioma(LGG)88.1%(37/42)vs.64.7%(22/34),χ²=5.919,P<0.05],and the high expression rate of HGG was significantly higher than that of LGG78.4%(59/76)vs.40.9%(9/22),χ²=8.449,P<0.05].The positive rate of PD-L1 in glioma group was significantly higher than that in control group51.3%(39/76)vs.12.5%(5/40),χ²=16.771,P<0.05].The positive rate of HGG was significantly higher than that of LGG61.9%(26/42)vs.38.2%(13/34),χ²=4.214,P<0.05],and the high expression rate of HGG was significantly higher than that of LGG50.0%(13/26)vs.7.7%(1/13),P<0.05].The expression of CMTM6 was significantly correlated with PD-L1(r=0.535,P<0.05).Western blotting results showed the expression of CMTM6 in glioma was higher than that in control group(1.04±0.51 vs.0.32±0.06,t=12.174,P<0.05),and that in HGG was higher than that in LGG(1.26±0.46 vs.0.78±0.44,t=4.641,P<0.05).The expression of PD-L1 in glioma was higher than that in the control group(0.68±0.57 vs.0.21±0.11,t=6.896,P<0.05),and that in HGG was higher than that in LGG(0.92±0.61 vs.0.38±0.32,t=4.963,P<0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with CMTM6/PD-L1 positive expression was worse than that of patients with negative expression(χCMTM62=5.371,χPD-L12=9.570,Log Rank P<0.05),and that of patients with high expression was worse than that of low expression(χCMTM62=7.282,χPD-L12=6.777,Log Rank P<0.05).Conclusion The expression of CMTM6/PD-L1 in glioma is obviously up-regulated,and there is a positive correlation between them.The expression intensity is closely related to the pathological grade of glioma,and the expression level is negatively related to the survival time.