HE4 Combined With CA125 For Monitoring The Recurrence Of Epithelial Ovarian Cancer And Its Related Research

Ovarian cancer is one of the most common gynecological malignancies,and epithelial ovarian cancer is the majority.The incidence of ovarian cancer is second only to cervical cancer and endometrial cancer,but the mortality rate is the highest among gynecological malignancies.In recent years,although surgical techniques have been improved and chemotherapy has been improved,the 5-year survival rate is only about 30%.The main reasons include the following: 1.The clinical symptoms of ovarian cancer are not typical.Most patients do not have obvious subjective symptoms,and their consciousness of physical examination on time is weak,hence 70% of the patients were diagnosed at advanced stage.2.Ovarian cancer develops rapidly.3.Ovarian cancer recurs frequently even after standardized treatment.Therefore,in addition to effective early diagnosis and treatment,it is particularly important to strengthen the management and monitoring of ovarian cancer patients after treatment,so as to detect recurrence timely and treat early.At present,carbohydrate antigen 125(CA125)is the most commonly used tumor marker in clinic,but it is also over expressed in many benign lesions(like pelvic inflammatory disease,endometriosis and so on),and there is a certain false positive rate.At the same time,CA125 is expressed normally in some ovarian cancer,we call it false negative rate.Human epididymal protein 4(HE4)is a new tumor marker,It has high expression in ovarian cancer,which has been approved for clinical use by the Food and Drug Administration of the United States.A large number of studies have shown that the sensitivity and specificity of HE4 in the diagnosis of epithelial ovarian cancer is better than that of CA125,however there is little research comparing the clinical value of the combination and independence use of the two indicators on diagnosing the recurrence of epithelial ovarian cancer.This study put an effort on it.Objectives: To evaluate the diagnostic value of HE4 combined with CA125 in monitoring the recurrence of epithelial ovarian cancer and the study of the recurrence of ovarian cancer,providing effective evidence for early detection and intervention of epithelial ovarian cancer recurrence.At the same time,the range of HE4 reference value is recalculated to serve the clinic.Methods: Patients who were diagnosed as ovarian cancer,treated with neoadjuvant chemotherapy according to their condition and confirmed epithelial ovarian cancer by pathology after satisfactory tumor cell reduction in our hospital in recent years were selected.Patients who do not need neoadjuvant chemotherapy can be operated directly.All the selected patients were treated with chemotherapy according to the first-line standard regimen after surgery.The changes of serum CA125 and HE4 were monitored throughout the treatment.The values of CA125 and HE4 in serum were measured at different follow-up time points after chemotherapy up to recurrence(imaging changes or confirmed recurrence of epithelial ovarian cancer by two operations)or 18 months after operation if no recurrence.A retrospective study was carried out on the disease progression of 49 patients enrolled.Results:1.The sensitivity of HE4 in detecting the recurrence of epithelial ovarian cancer is better than that of CA125(P<0.001).There is no significant difference in the specificity of HE4 used to detect the recurrence of epithelial ovarian cancer compared to CA125(P=0.071).The sensitivity of HE4 combined with CA125 used to detect the recurrence of epithelial ovarian was 80%,and the specificity was 100%.2.The positive rate of HE4 combined with CA125 were higher than that of HE4 or CA125,but there was no significant difference(P=0.081).3.The diagnostic value of HE4 as tumor marker for monitoring the recurrence of epithelial ovarian cancer was better than that of CA125(area under the operating characteristic curve of HE4 was 0.822,P=0.002,area under the operating characteristic curve of CA125 was 0.781,P=0.006.The critical value of HE4 is 94.66pmol/L,at this time the sensitivity is 66.67% and the specificity is 86.67%.4.The level of serum HE4 and CA125 in patients with relapse showed an upward trend before the recurrence of imaging diagnosis.When CA125 reference value was 35U/ml and HE4 reference value was 70pmol/L,serum HE4 level increased 9 months before recurrence,serum CA125 level increased at 3 months before recurrence,and HE4 was 6 months ahead of CA125.If the reference value of HE4 was obtained according to this study,35U/ml was taken according to the reference value of CA125,the reference value of HE4 was 94.66pmol/L,the level of serum HE4 increased 6 months before the recurrence,the serum CA125 level increased 3 months before the recurrence,and HE4 was 3 months ahead of CA125.Serum HE4 and CA125 levels fluctuated within normal range without recurrence.5.Advanced cancer is more likely to relapse than early cancer(P=0.03).6.The menstrual condition of patients is not statistically significant(P=0.5).Conclusions:1.As a tumor marker,the diagnostic value of HE4 on detecting the recurrence of epithelial ovarian cancer is higher than that of CA125,and its sensitivity is better than CA125,but its specificity is relatively poor.The combine use of the two markers may be more effective than single use of HE4 or CA125 in monitoring the recurrence of epithelial ovarian cancer,which is of great significance in prolonging the survival time of epithelial ovarian cancer patients after surgery.2.According to the ROC curve,When the cut-off value of HE4 is 94.66pmol/L,the sensitivity is 66.67% and the specificity is 86.67%.When serum HE4 level is higher than this threshold,the possibility of recurrence of ovarian cancer is significantly increased.3.The level of serum HE4 and CA125 increased before recurrence,and the time of abnormal appearance was earlier than that of imaging,and HE4 was 3-6 months ahead of CA125.Compared with the longer time,the recurrence was predicted,and the time limit of 3-6 months was not affected by timely intervention treatment,and the mental burden and psychological pressure of the patients were reduced.The results suggest that setting HE4 for 94.66pmol/L is suitable for clinical monitoring.4.the more late the clinical stage of ovarian cancer patients,the more easy to relapse.In addition,there was no significant Statistical difference between the patiens who are in menopause or not and the patiens whose tumor recrudesce.