The Value Of CA125, HE4, RMI1 And ROMA In Diagnosis Of Ovarian Epithelial Malignant Tumor

Background and Objective Because the ovary is located in the deep part of the pelvis, it is not easy to be found in the early stage of ovarian malignant tumor.The diagnosis rate is very low. There are many distant metastasis in the late stage of ovarian malignant tumor, lacking of effective treatment. Therefore, the malignant tumor of the ovary has become the main disease threatening of the life and health of women. Early detection and diagnosis of malignant ovarian tumor, radical surgical treatment is the fundamental to improve the prognosis of patients. At present, the methods of differential diagnosis of ovarian tumors commonly used in clinic are serological markers, imaging examination, vagino-recto-abdominal examination. The gold standard for diagnosis is pathological examination. Serum cancer antigen 125(CA125), a high molecular weight glycoprotein, is highly expressed in epithelial ovarian malignant tumor cells. It is the most widely used epithelial ovarian malignant tumor markers currently in the world.It is widely used in differential diagnosis of ovarian tumor, treatment monitoring disease progression andprognosis, especially in monitoring curative effect quite sensitive in clinic. CA125,however, is not the ideal tumor marker. The value of CA125 in 50% patients with early malignant ovarian tumor is in the normal range, which is not significantly increased. The value of CA125 in the serum of some patients with benign ovarian tumors and non ovarian tumors will also increase. In recent years, human epididymis protein 4 has become a new type of tumor markers in the prediction of the risk of ovarian malignant tumor. Serum human epididymis secreted proteins 4(HE4) gene was first found in the human epididymis epithelial cell gene. HE4 gene in ovarian cancer tissues, especially highly expresses in the size of uterine endometrial epithelial ovarian cancer, but does not express in adjacent normal tissues and in early ovarian cancer tissue is up-regulated expression of different degrees, which are related to the occurrence of ovarian cancer. Foreign studies established mathematical model: risk of malignancy index(RMI), ovarian malignant tumor risk model(ROMA), combined with serology markers, ultrasound, menopausal status. Risk of malignancy index is calculated through the mathematical models of the value of serum CA125, ultrasound score, menopausal status into the equation, to predict the risk of the epithelial ovarian malignant tumors. Malignancy risk model(ROMA), the model forecast the risk of epithelial ovarian tumors by combining serum CA125, HE4, menopausal status together. Currently the related research about CA125, HE4 and RMI and ROMA two mathematical model predicting the risk of malignancy of pelvic messes is rare at home or abroad. The purpose of this study is to investigate the predictive value of CA125, HE4, RMI1 and ROMA in order to improve the accuracy of diagnosis of malignant ovarian epithelial tumor.Materials and methods 1 Research object Taking the 93 patients who were diagonosed with a pelvic mass and intended to receiving surgical treatment in the department of Obstetrics and Gynecology of the Second Affiliated Hospital of Zhengzhou University since April 2013 to June 2015 as the object of the research. All the patients completed abdominal ultrasound ortransvaginal ultrasound, computer tomography(CT) or magnetic resonance imaging(MRI) if necessary. The serum levels of HE4 and CA125 were detected by chemiluminescence before operation in all the patients.The gold standard for the diagnosis of postoperative was pathological sections, 43 cases were confirmed as epithelial ovarian malignant tumor. 50 cases were confirmed as benign disease,including 26 cases of ovarian endometriosis cyst, 24 cases of benign tumor. According to the International Federation of Gynecology and Obstetrics(FIGO 2006) surgical pathology staging criteria, 20 cases of ovarian malignant tumors were belong to stage I or II, 23 cases of ovarian malignant tumors were belong to stage IV or III. 2 Experimental methods The serum levels of CA125 and HE4 were measured by the electrochemical luminescence method, and the menopausal status of the patients was evaluated. The RMI value of each patient was calculated according to the calculation method of RMI1=U�M�CA125. U represents abnormal ultrasound examination results score.M represents menopausal status score. The value of CA125 were directly put into the formula for calculation. The cutoff value of RMI1 was 200. ROMA were calculated in both premenopausal and postmenopausal patients according to different menopausal status. The cutoff value of ROMA in premenopausal was 11.4%. The cutoff value of ROMA in postmenopausal patients was 29.97%. 3 Statistical methods All data were analysised by Statistics IBM SPSS21.0 statistical software. Measurement data tested for normality and Kolmogorov-Smirnov. For the measurement data which is in conformity with the normal distribution, it is described by mean of plus or minus standard deviation. The four quantile and median description was used for that was not conform to the normal distribution of the data.The rank sum test of non parametric test is used in the non parametric test. The two groups were compared using independent samples t test, The diagnostic efficacy of each index was evaluated through the receiver operating characteristic curve(ROC) and the area under the curve(AUC). P<0.05 was statistically significant, ?=0.05 as test standards.Results1. Serum CA125 expression levels of ovarian benign disease group and malignant tumor group respectively were(27.20,15.61~75.05),(315.70, 37.47~1115.00). The expression levels of serum HE4 respectively were(58.57, 49.46~72.95),(786.00, 100.50~890.00). Serum levels of CA125 and HE4 were compared between the two groups, the differences were statistically significant(P < 0.01). 2. The expression levels of serum CA125 of endometriosis cysts group and benign ovarian tumor group respectively were(72.14,42.01~51.37),(16.27,11.48~22.02). The expression levels of serum HE4 of the two groups respectively were 63.45�13.54 and 58.37�13.25. The level of serum CA125 were compared between the two groups,the differences were statistically significant(P < 0.01). The level of serum HE4 were were compared between the endometriosis cysts group and benign ovarian tumor group, the differences were of no statistically significant(P > 0.05). 3. The expression levels of serum CA125 in the premenopausal and postmenopausal women with benign ovarian disease respectively were(27.2,15.61~75.05),(11.46,7.80~45.06). The expression levels of serum HE4 in the premenopausal and postmenopausal women with benign ovarian disease respectively were 59.84�14.42, 66.54�6.68. There were significant differences between the premenopausal and postmenopausal women with benign disease in levels of serum CA125(P<0.05), and there was no significant difference in levels of HE4(P>0.05). The serum levels of CA125 in premenopausal and postmenopausal group with malignant ovarian tumor group respectively were(54.72, 21.25~1125.70),(464.30, 51.61~10.84). The serum levels of HE4 in premenopausal and postmenopausal group with malignant ovarian tumor group respectively were(135.60, 63.46~890.00),(78.6, 258.00~890.00).The serum levels of CA125 in premenopausal or postmenopausal women were of no significant difference in the malignant tumor group(P>0.05). The serum levels of HE4 in premenopausal or postmenopausal women were of no significant difference in the malignant tumor group(P>0.05). 4. The serum levels of CA125 in ovarian malignant tumor group staging I or II and III or IV respectively were(35.76, 14.89~293.98),(880.40, 203.60~2153.00).The serum levels of HE4 in ovarian malignant tumor group staging I or II and III or IV respectively were(101.15,62.00~890.00),(789.00,719.70~990.00).The expression levels of serum CA125 and HE4 in the two groups were compared, and the difference were statistically significant(P<0.05). 5. The sensitivity, specificity, positive predictive value and negative predictive value of RMI1 and ROMA in the premenopausal status group respectively were 70.73%, 60%, 87.87%, 86.36%, 88.46%, 51.36%, 88.46%. The sensitivity, specificity, positive predictive value and negative predictive value of RMI1, ROMA in postmenopausal women were 85.71%, 77.78%, 90%, 70%, 90.47%, 88.89% and 95% and 80%. 6. The area below the curve represented by CA125, HE4, RMI and ROMA is shown below: CA125:0.813(95%CI 0.746~0.916), HE4:0.874(95%CI 0.782~0.967), RMI1:0.891(95%CI 0.819~0.962), ROMA:0.912(95%CI 0.842~0.981). Comparing the area under the curve as follows: ROMA>RMI1>HE4>CA125.Conclusions 1. HE4, CA125 can be used as a biological marker to distinguish ovarian epithelial malignant tumor.And HE4 has a higher accuracy than CA125 in the differential diagnosis of ovarian endometriosis. Detecting of HE4 and CA125 can improve the diagnosis rate of ovarian epithelial malignant tumor. 2. The expression levels of serum HE4 and CA125 in patients with ovarian malignant tumor is closely related to the type of ovarian tumor, which is high in the serum of epithelial ovarian cancer patients. And levels of serum HE4, CA125 are closely related to surgical pathology staging.The expression levels of serum HE4, CA125 reflect occurrence, development and diffusion of ovarian epithelial malignant tumor in a certain level. 3. Comparison of RMI1 and ROMA in the diagnosis of ovarian epithelial malignant tumor in premenopausal and postmenopausal women show that ROMA has higher accuracy. 4. The diagnostic efficacy of ROMA, RMI1 are superior to CA125 or HE4 detection alone. The diagnosis efficiency of HE4 is better than CA125. The diagnosis of ovarian epithelial malignant tumor of ROMA has the highest efficiency.