Prediction Of Lymph Node Metastasis In Endometrial Carcinoma By Serum Carbohydrate Antigen 125 And Human Epididymal Protein 4:a Meta-analysis

Objective:Predictive value analysis of serum carbohydrate antigen 125(CA125)and human epididymal protein 4(HE4)in endometrial carcinoma(EC)lymph node metastasis.Methods:Comprehensive search of Chinese and English databases:CNKI,Wanfang Database,Weip Database,CBM,Pub Med,the Cochrane Library and EMBASE was conducted to collect all relevant literatures published in the database until December 2021.Keywords:Carbohydrate antigen 125;Human epididymal protein 4;CA125;HE4;Endometrial carcinoma;Lymph node metastasis.The literatures on serum CA125 and HE4 predicting EC lymph node metastasis were comprehensively searched,and the qualified literatures were screened strictly according to the criteria and data were extracted.Then,QUADAS-2 table was used to evaluate the literature quality.STATA 16.0 software was used for statistical analysis,and combined sensitivity(Sen)and specificity(Spe)were used to evaluate the predictive value of serum CA125 and HE4.Results:There were 14 literatures in total,and the total sample size was 2270cases,including 355 cases in the endometrial carcinoma lymph node metastasis group and 1915 cases in the endometrial carcinoma lymph node non-metastasis group.Heterogeneity analysis showed that the heterogeneity caused by serum CA125,HE4and HE4+CA125 was not caused by threshold effect.serum CA125(Sensitivity I~2=71.20%,Q=45.13,P<0.05;Specificity I~2=85.68%,Q=90.76,P<0.05),serum HE4(Sensitivity I~2=49.93%,Q=25.96,P<0.05;Specificity I~2=89.03%,Q=118.48,P<0.05),serum HE4+CA125(Sensitivity I~2=58.73%,Q=14.54,P<0.05;Specificity I~2=83%,Q=37.27,P<0.05),so the random effect model was used for the combined effect sizes.The combined effect results showed that sensitivity and specificity of serum CA125,HE4 and HE4+CA125 were 0.60[95%CI(0.51,0.69)]and 0.78[95%CI(0.72,0.83)];0.66[95%CI(0.58,0.74)]and 0.80[95%CI(0.75,0.85)];0.76[95%CI(0.64,0.85)]and 0.82[95%CI(0.76,0.88)],respectively.Positive likelihood ratio and negative likelihood ratio of serum CA125,HE4 and HE4+CA125 for endometrial carcinoma lymph node metastasis were 2.74[95%CI(2.24,3.36)]and 0.51[95%CI(0.42,0.62)];3.32[95%CI(2.57,4.29)]and 0.42[95%CI(0.34,0.53)];4.28[95%CI(3.03,6.05)]and 0.29[95%CI(0.19,0.45)],respectively.The diagnostic odds ratio of serum CA125,HE4 and HE4+CA125 for predictive of endometrial carcinoma lymph node metastasis were 5.40[95%CI(3.94,7.41)],7.84[95%CI(5.15,11.94)],14.61[95%CI(7.88,27.10)],respectively.The area under the SROC curve of serum CA125,HE4 and HE4+CA125 in predictiving endometrial carcinoma lymph node metastasis were 0.76[95%CI(0.72,0.79)],0.79[95%CI(0.75,0.82)]and 0.86[95%CI(0.83,0.89)],respectively.The Deeks funnel plots of serum CA125,HE4 and HE4+CA125showed symmetrical distribution,with Probability values greater than 0.05,indicating that there was no publication bias in all the 14 literatures.Conclusion:The accuracy of serum HE4+CA125 in predicting endometrial carcinoma lymph node metastasis was higher than that of serum CA125 or HE4,and the accuracy of serum HE4 in predicting endometrial carcinoma lymph node metastasis was higher than that of serum CA125.In conclusion,the combination of the two has higher predictive value.