外周血单个核细胞GTSE1水平与上皮性卵巢癌预后的相关性

Correlation between GTSE1 levels in peripheral blood mononuclear cells and the prognosis of epithelial ovarian cancer

目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后的关系。选择2017年04月至2020年10月本院126例EOC患者(EOC组)和40例同期无EOC的健康体检者(对照组)作为研究对象。Ficoll密度梯度离心法分离外周血中单个核细胞,蛋白质免疫印迹法检测GTSE1水平。Spearman相关分析EOC组织和外周血单个核细胞中GTSE1水平的关系。随访了解EOC预后,用COX回归分析EOC预后的风险因素。结果:GEPIA和Kaplan-Meier Plotter分析结果显示,卵巢癌组织中GTSE1水平高于正常卵巢组织(P<0.05),GTSE1低水平卵巢癌患者的中位无进展生存时间高于GTSE1高水平卵巢癌患者(P<0.05)。随访期间复发98例(77.8%),其中铂类敏感型65例,铂类耐药型33例;死亡41例(32.5%)。EOC组的外周血单个核细胞中GTSE1 mRNA和GTSE1蛋白水平均高于对照组(P<0.001)。EOC患者癌组织和外周血单个核细胞中GTSE1水平呈正相关关系(r_(s)=0.225,P=0.011)。国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ-Ⅱ期患者的GTSE1水平低于Ⅲ-Ⅳ期的患者(P<0.001);未复发患者的GTSE1水平低于铂类敏感型和铂类耐药型的患者(P<0.05);生存患者的GTSE1水平低于死亡患者(P<0.001)。GTSE1高水平患者的无复发生存时间和总生存时间均低于GTSE1低水平患者(P<0.001)。COX回归分析结果显示,FIGO分期高(HR=2.110,95%CI:1.465~3.038,P<0.001;HR=2.261,95%CI:1.212~4.216,P=0.011)、初次手术残存灶>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012;HR=2.465,95%CI:1.246~4.874,P=0.010)和GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002;HR=5.634,95%CI:2.410~13.169,P<0.001)是EOC预后(复发和生存)的独立危险因素,应用贝伐单抗(HR=0.293,95%CI:0.116~0.738,P=0.010;HR=0.141,95%CI:0.056~0.357,P<0.001)是EOC预后的独立保护因素。结论:EOC患者外周血单个核细胞中GTSE1水平高提示预后不良风险高。

Objective:To investigate the relationship between G_(2)and S phase-expressed-1(GTSE1)in peripheral blood mononuclear cells and the prognosis of epithelial ovarian cancer(EOC).Methods:GEPIA and Kaplan-Meier Plotter were used to analyze the expression of GTSE1 in ovarian cancer tissues and its relationship with prognosis.126 patients with EOC(EOC group)in our hospital from April 2017 to October 2020 and 40 healthy check-ups without EOC(control group)during the same period were selected as study subjects.Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation.GTSE1 level was detected by Western blotting.Spearman correlation analysis of the relationship between GTSE1 level in EOC tissues and GTSE1 level in peripheral blood mononuclear cells was performed.The prognosis of EOC was monitored,and the risk factors for the prognosis of EOC were analyzed using COX regression.Results:GEPIA and Kaplan-Meier Plotter analysis showed that the level of GTSE1 in ovarian cancer tissues was higher than that in normal ovarian tissues(P<0.05),and the median progression-free survival time of ovarian cancer patients with low level of GTSE1 was higher than that of ovarian cancer patients with high level of GTSE1(P<0.05).During follow-up,98 cases(77.8%)relapsed,including 65 cases of platinum-sensitive type and 33 cases of platinum-resistant type.41 cases(32.5%)died.GTSE1 mRNA and GTSE1 protein level in peripheral blood mononuclear cells were higher in the EOC group than that in the control group(P<0.001).There was a positive correlation between GTSE1 level in cancer tissues and GTSE1 level in peripheral blood mononuclear cells of EOC patients(r_(s)=0.225,P=0.011).The level of GTSE1 in patients with stageⅠ-Ⅱaccording to International Federation of Gynecology and Obstetrics(FIGO)was lower than that in patients with stageⅢ-Ⅳ(P<0.001).The level of GTSE1 in non-relapsed patients was lower than that in platinum-sensitive and platinum-resistant patients(P<0.05).The level of GTSE1 in survival patients was lower than that in death patients(P<0.001).The recurrence-free survival time and overall survival time of patients with high GTSE1 level were lower than those of patients with low GTSE1 level(P<0.001).COX regression analysis showed that high FIGO stage(HR=2.110,95%CI:1.465~3.038,P<0.001.HR=2.261,95%CI:1.212~4.216,P=0.011),initial surgical residual foci>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012.HR=2.465,95%CI:1.246~4.874,P=0.010)and GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002.HR=5.634,95%CI:2.410~13.169,P<0.001)were independent risk factors for EOC prognosis(recurrence and survival),and bevacizumab(HR=0.293,95%CI:0.116~0.738,P=0.010.HR=0.141,95%CI:0.056~0.357,P<0.001)was an independent protective factor for EOC prognosis.Conclusion:High level of GTSE1 in peripheral blood mononuclear cells from EOC patients suggests a high risk of poor prognosis.