Application Of Serum Ferritin Combined With CA125 Or HE4 In The Diagnosis Of Epithelial Ovarian Cancer

Aims: Ovarian cancer is one of the most common malignant tumors in gynecology,and the mortality rate is the highest in all malignant tumors.At present,the screening of ovarian cancer mainly depends on imaging and tumor markers.Serum CA125 is a common tumor marker for ovarian cancer and is one of the prognostic indicators of epithelial ovarian cancer.CA125 has poor sensitivity and low specificity for detecting ovarian cancer in early stages.Serum ferritin is elevated in many malignancies,such as breast cancer,hepatocellular cancer,non-Hodgkin's lymphoma,renal cell cancer,breast cancer,pancreatic cancer and stomach cancer.Human epididymis protein 4(HE4)is another highly recognized marker of epithelial ovarian cancer(EOC)after CA125.In the present study,we evaluated the performance of ferritin as a diagnostic tool to detect epithelial ovarian cancer.Methods: In this study we recruited from patients presenting to the Department of Gynecology,the Affiliated Hospital of Qingdao University and Women & Children?s Healthcare Hospital of Linyi.Random selection of 70 cases of healthy control,70 cases of pathologic diagnosis of gynecologic benign diseases and 124 cases of pathologic diagnosis of epithelial ovarian cancer.Each group had corresponding diagnostic criteria and exclusion criteria.Written informed consent was obtained from all the donors,and the study was approved by the Affiliated Hospital of Qingdao University Ethics Committee.Serum ferritin,HE4 and CA125 levels were detected in each group.The relationship between serum ferritin,HE4,CA125 and each of the clinic pathological parameters was analyzed.The diagnostic accuracy of ferritin,HE4 and CA125 in discriminating ovarian cancer were determined.Results: Serum ferritin,HE4 and CA125 was higher in patients with EOC compared to HCs and patients with benign genital neoplasms.Ferritin was not correlated with CA125 or HE4 in benign ovarian diseases(Spearman r =0.095,P=0.086),healthy controls serum cohorts(Spearman r =0.13,P =0.067),and EOC(Spearman r =0.083,P = 0.094).Therefore,there is no relationship between circulating levels of ferritin and CA125.Ferritin was also not associated with HE4 in benign ovarian diseases(Spearman r =0.092,P =0.087),healthy controls(Spearman r=0.17,P =0.078),and EOC(Spearman r =0.079,P = 0.091).To evaluate the diagnostic accuracy of serum ferritin,HE4 and CA125 for prediction of EOC among the different donor groups,we performed receiver operating characteristic(ROC)analyses,and then compared the area under the ROC curves(AUCs)for ferritin,HE4 and CA125.For discriminating between HCs and EOC,ferritin,HE4 and CA125 could discriminate HC from EOC(P<0.05).Ferritin showed better diagnostic accuracy for EOC in the early stages when compared with CA125 or HE4 alone(p = 0.002,0.038);CA125 showed better diagnostic accuracy for EOC in the advanced stages when compared with ferritin or HE4 alone(P = 0.026,).A combination of ferritin and CA125 or HE4 increases the diagnostic accuracy to discriminate EOC from HCs.Conclusions: Ferritin was able to discriminate between HCs and EOC patients,especially in early-stage disease.The combination of serum ferritin and CA125 or HE4 provides the higher diagnostic accuracy to screen for EOC and,in particular,to detect early stages of EOC.Serum ferritin could serve as a valuable EOC biomarker to complement the standard CA125 test.