Clinical Diagnostic Value Of Combined Detection Of Serum Or Urinary Bcl-2 With Serum CA125 In Ovarian Epithelial Cancer

Background and purposeOvarian cancer is one of a gynecological malignancy tumor, whose mortality rates are almost highest. And in recent years its incidence rise significantly. The main reasons are absence of clinical symptom in early stage, and lack of early diagnostic methods.70%～80% of ovarian cancer was found in late stage and only 20%～30% have 5 year survival rate. But the 5-year survival rate in early-stage ovarian cancer can reach to 90% without postoperative chemotherapy. So we need to find a simple and reliable method for early diagnosis of ovarian cancer, it will have a high value in clinical applications. CA125 is a form of mucous glycoprotein, which is generally used to diagnose the advanced ovarian cancer, especially to monitor the ovarian cancer recurrence. But when it is used in the diagnosis of early stage ovarian cancer the sensitivity and specificity are low, and the positive result (presence of serum CA125) only went to 50% of patients with early stage ovarian cancer. CA125 level can also be elevated in healthy women, benign ovarian tumor and the benign ovarian related disease in serum. BCL-2 gene (apoptosis suppressor genes) is a kind of cell cycle plays an important role in human genes, and various forms of tumor with excessive expression. There are a lot of reports about BCL-2 in ovarian tissue, but the report in serum and urine is rare. This study adopts enzyme-linked immunosorbent method (ELISA) to detect the urine and serum levels of BCL-2 and CA125 in epithelial ovarian cancer patients, to preliminary discuss the value of BCL-2 as epithelial ovarian tumor markers, and the value for ovarian cancer screening.Materials and methodsExperimental samples:we collected 50 epithelial ovarian cancer cases with pathology diagnosis in the first affiliated hospital of zhengzhou university from Jan 2008 to Mar 2009 according to FIGO (2000):16 cases of the stagesⅠ/Ⅱperiod,34 cases of the stagesⅢ/Ⅳperiod; 32 cases of the serous carcinoma,18 cases of the mucinous carcinoma aged 46.5±11.9 (32～72). We detected 20 cases of benign epithelial ovarian tumor hospitalized in the first affiliated hospital of zhengzhou university aged 42.9±8.9 (30～65). We detected 18 cases of normal women in control group, from the first affiliated hospital of zhengzhou university aged 44.6±7.8(30～60). All of the cases have except bone tumor or other tumors.We phlebotomize 4ml fasting blood from patients (specimens before radiation and chemotherapy or other treatment), all of the blood specimen were saved in clean tubes coagulated for 30min in room temperature, and then centrifugalized in 4 degrees Celsius,3000r/min, for 15min. We got upper serum into EP tube freeze-stored in-70℃refrigerator. We acquired 5ml fasting urine and then got upper urine into EP tube freeze-stored in-70°c refrigerator after 5min centrifugalized. It is the same to the controls.Experimental methodsWe detected the bcl-2 level in serum and urine using ELISA. Fluctuation alert was got from normal healthy women (±1.96S), after calculation upper threshold of urine is 55U/ml, upper threshold of serum is 18U/ml. We detected the serum level CA125 using ELISA with the kit bought from ADL, strictly according to the company's operation manual kit. The upper threshold is 35U/ml.The data were processed SPSS 13.0 statistical software. Comparison between the two groups with t-test, Comparison between groups compared with more than mean variance analysis and K-W rank sum test, counted datas were used x2 test the rate of using x2 test analysis. Simultaneously sensitivity (Se), specificity (Sp) were analysisted.Results1 Bcl-2 levels in serum and urine of ovarian cancer patients respectively were (35.96±17.96)U/ml, (149.61±83.46)U/ml, bcl-2 levels in serum and urine of ovarian benign tumor patients respectively were (13.63±4.28)U/ml, (44.93±15.39)U/ml; Bcl-2 levels in serum and urine of control group were (11.86±4.9)U/ml, (33.43±13.05)U/ml. Three groups have significant difference in bcl-2 level (p<0.05). Ovarian cancer group was higher than the other two groups (p<0.05). There was no significant difference between Patients with ovarian benign tumor and control group in serum bcl-2(p>0.05).But there was significant difference in urine bcl-2 (p<0.05). Serum CA125 was(675.31±123.7) U/ml in ovarian cancer group, was (24.92±7.2) U/ml in ovarian benign tumor group, was (19.13±5.5) U/ml in normal control group. Three groups have significant difference in serum CA125. There was significant difference between Patients with ovarian cancer group and ovarian benign tumor group (p<0.05), there was no significant difference between Patients with ovarian benign tumor and control group (p>0.05).2 The sreum and urine bcl-2 levels of early-stage ovarian cancer(Ⅰ～Ⅱ)were (22.18±10.83)U/ml, (91.68±52.07)U/ml, and that of advanced-stage(III IV)were(42.44±17.26)U/ml, (175.40±82.46)U/ml, there were significant difference in two groups (p<0.05); The serum and urine bcl-2 levels in patients with ovarian serous cystadenocarcinoma were (36.72±18.22)U/ml, (147.56±81.09)U/ml, and that of ovarian mucinous cystadenocarcinoma were (34.61±18.33)U/ml, (150.48±89.89) U/ml, and there was no significant difference in two groups (p>0.05).3 The bcl-2 positive rate of serum and urine sensitivity were up to 43.7% and 50% in early-stage ovarian cancer, which were up to 68.9% and 75.9% in advanced-stage, all the difference have statistics significance (p<0.05). The bcl-2 positive rate in ovarian serous cystadenocarcinoma were up to 68.75% and 75%. The positive rate were up to 66.67% and 77.78% in ovarian mucinous cystadenocarcinoma, all with the difference non-statistics significance (p>0.05). The positive rate of serum CA125 was up to 62.5% in early-stage ovarian cancer, and that of advanced-stage was up to 91.18%, the difference have statistics significance (p<0.05), and the difference have statistics significance (p<0.05).Between the ovarian serous cystadenocarcinoma and ovarian mucinous cystadenocarcinoma.4 The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, Youden's index, positive predictive value, negative predictive value of serum bcl-2 are 68%,84.21%,4.31,0.38,0.52,85%,66.67%. They are 76%,89.47%,7.22,0.27, 0.65,90.48%,73.91% of urine bcl-2. They are 82%,73.68%,3.12,0.24,0.56, 80.39%,75.68% of serum CA125. They are 86%,86.64%,6.53,0.16,0.73,86%, 82.50% of serum bcl-2 with serum CA125. They are 94%,94.74%,17.87,0.06,0.89, 95.92%,92.31% of urine bcl-2 with serum CA125. They are 96%,97.37%,36.5,0.04, 0.93,97.96%,94.87% of sreum and urine bcl-2 with serum CA125.Conclusions1 Bcl-2 levels and the diagnostic evaluation index were higher in serum and urine, combined with the detection of serum CA125 the levels and the diagnostic evaluation index were significantly improved. so they have important value, might be used as epithelial ovarian cancer tumor marker.2 Bcl-2 detected in urine than serum tumor markers was more user-friendly and accessible, suggesting tumor markers of urine has important significance in ovarian cancer screening.