血清甘露聚糖结合凝集素相关蛋白19和三叶因子3及精子相关抗原9水平对宫颈癌患者术后2年复发的预测价值

Values of serum levels of MAP19,TFF3and SPAG9to the prediction of recurrence two years after operation in cervical cancer patients

目的观察宫颈癌患者血清甘露聚糖结合凝集素相关蛋白19(mannose-binding lectin associated protein 19,MAP19)、三叶因子3(trefoil factor 3,TFF3)、精子相关抗原9(sperm-associated antigen 9,SPAG9)表达情况,探讨其对宫颈癌患者术后2年复发的预测价值。方法120例行手术治疗的宫颈癌患者为宫颈癌组,120例低级别宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)患者为CIN组,120例子宫肌瘤或子宫腺肌症患者为对照组。采用ELISA法检测3组血清MAP19、TFF3、SPAG9水平并进行比较。宫颈癌患者术后随访2年,根据复发情况分为复发组40例和未复发组80例,比较2组淋巴结转移、FIGO分期等临床资料及血清MAP19、TFF3、SPAG9水平;采用多因素logistic回归分析宫颈癌患者术后2年复发的影响因素;绘制ROC曲线,评估血清MAP19、TFF3、SPAG9预测宫颈癌患者术后2年复发的效能。结果宫颈癌组血清MAP19[(266.07±80.27)μg/L]、TFF3[(407.27±91.45)μg/L]、SPAG9[(124.09±20.41)μg/L]水平均高于CIN组[(200.27±81.28)、(314.66±70.41)、(106.83±13.29)μg/L]、对照组[(130.25±48.27)、(218.61±50.83)、(3.21±1.07)μg/L](P<0.05),CIN组均高于对照组(P<0.05)。复发组有淋巴结转移(87.50%)、FIGO分期ⅡA期(47.50%)、肿瘤最大直径≥4cm(62.50%)比率及血清MAP19[(199.12±75.48)μg/L]、TFF3[(398.04±90.27)μg/L]、SPAG9[(131.73±19.93)μg/L]水平均高于未复发组[17.50%、15.00%、30.00%、(129.48±50.71)μg/L、(196.65±50.16)μg/L、(10.28±2.31)μg/L](P<0.05)。淋巴结转移(OR=3.054,95%CI:1.367~6.511,P<0.001)、FIGO分期(OR=2.136,95%CI:1.082~4.695,P<0.001)、肿瘤最大直径(OR=1.509,95%CI:1.204~3.165,P=0.020)及血清MAP19(OR=5.841,95%CI:4.749~10.231,P<0.001)、TFF3(OR=4.202,95%CI:2.540~6.394,P<0.001)、SPAG9(OR=4.183,95%CI:3.705~6.247,P<0.001)水平是宫颈癌患者术后2年复发的影响因素。血清MAP19、TFF3、SPAG9分别以189.05、311.25、107.40μg/L为最佳截断值,单独及联合预测宫颈癌患者术后2年复发的AUC分别为0.850(95%CI:0.713~0.935,P<0.001)、0.817(95%CI:0.750~0.916,P<0.001)、0.795(95%CI:0.694~0.910,P<0.001)、0.931(95%CI:0.840~0.958,P<0.001),灵敏度分别为95.1%、93.2%、89.3%、95.6%,特异度分别为74.0%、77.1%、76.8%、80.4%。结论有淋巴结转移、FIGO分期ⅡA期、肿瘤最大直径≥4cm及血清MAP19、TFF3、SPAG9水平升高的宫颈癌患者术后2年易复发,血清MAP19、TFF3、SPAG9联合预测宫颈癌患者术后2年复发有较高价值。

Objective To observe the expressions of serum mannose-binding lectin associated protein 19(MAP19),trefoil factor 3(TFF3)and sperm-associated antigen 9(SPAG9)in patients with cervical cancer,and to investigate their values to the prediction of recurrence two years after operation.Methods The levels of serum MAP19,TFF3and SPAG9were detected by ELISA and compared in 120patients with cervical cancer(cervical cancer group),120patients with cervical epithelial sarcoma(CIN group),and 120patients undergoing total hysterectomy due to uterine leiomyopathy and adenomyosis(control group).Cervical cancer group was redivided into recurrence group(n=40)and non-recurrence group(n=80),and were compared the lymph node metastasis,FIGO stage,and levels of MAP19,TFF3and SPAG9.Multivariate logistic regression was used to analyze the influencing factors of recurrence of cervical cancer two years after operation.ROC curve was drawn to evaluate the predictive efficiencies of serum MAP19,TFF3and SPAG9on the recurrence of cervical cancer two years after operation.Results The levels of MAP19,TFF3and SPAG9were higher in cervical cancer group[(266.07±80.27),(407.27±91.45),(124.09±20.41)μg/L]than those in CIN group[(200.27±81.28),(314.66±70.41),(106.83±13.29)μg/L]and control group[(130.25±48.27),(218.61±50.83),(3.21±1.07)μg/L](P<0.05),and higher in CIN group than those in control group(P<0.05).The percentages of patients with lymph node metastasis,FIGO stageⅡA and tumor diameter≥4cm,as well as the levels of MAP19,TFF3 and SPAG9 were higher in recurrence group[87.50%,47.50%,62.50%,(199.12±75.48)μg/L,(398.04±90.27)μg/L,(131.73±19.93)μg/L]than those in non-recurrence group[17.50%,15.00%,30.00%,(129.48±50.71)μg/L,(196.65±50.16)μg/L,(10.28±2.31)μg/L](P<0.05).Lymph node metastasis(OR=3.054,95%CI:1.367-6.511,P<0.001),FIGO stage(OR=2.136,95%CI:1.082-4.695,P<0.001),tumor maximum diameter(OR=1.509,95%CI:1.204-3.165,P=0.020),serum MAP19 level(OR=5.841,95%CI:4.749-10.231,P<0.001),TFF3level(OR=4.202,95%CI:2.540-6.394,P<0.001),and SPAG9level(OR=4.183,95%CI:3.705-6.247,P<0.001)were the influencing factors of recurrence of cervical cancer two years after operation.When the optimal cut-off values of serum MAP19,TFF3and SPAG9were 189.05,311.25and 107.40μg/L,the AUCs of single and combined detection of them three for predicting recurrence of cervical cancer two years after operation were 0.850(95%CI:0.713-0.935,P<0.001),0.817(95%CI:0.750-0.916,P<0.001),0.795(95%CI:0.694-0.910,P<0.001),and 0.931(95%CI:0.840-0.958,P<0.001),the sensitivities were 95.1%,93.2%,89.3%and 95.6%,and the specificities were 74.0%,77.1%,76.8%and 80.4%,respectively.Conclusion Cervical cancer is prone to recur two years after operation in patients with lymph node metastasis,FIGO stageⅡA,tumor diameter≥4cm and elevated serum levels of MAP19,TFF3and SPAG9,and the combined detection of MAP19,TFF3and SPAG9has a high predictive value.