Serum MiR-125b Levels Are Associated With Epithelial Ovarian Cancer(EOC) Development And Treatment Responses

Objective:To study whether the change of serum miR-125b level is related to the occurrence and development of epithelial ovarian cancer(EOC),to demonstrate whether serum miR-125b level is related to diagnosis and treatment response of epithelial ovarian cancer;and to prove that serum miR-125b can be used as a biomarker for diagnosing and predicting the treatment response of epithelial ovarian cancer patients.Methods:A total of 259 patients,including 42 healthy controls,30 benign ovarian tumors,35 borderline epithelial ovarian tumors and 152 epithelial ovarian cancers,were collected from the Affiliated Hospital of Qingdao University from February 2010 to October 2014.The level of serum miR-125b was measured by RT-qPCR(real-time fluorescence quantitative detection),and the relationship between serum miR-125b and benign tumors in EOC patients was analyzed We assessed the changes of serum miR-125b in different biological characteristics of epithelial ovarian cancer,especially in patients with advanced FIGO(stage III+IV)and early FIGO(stage I+II)and patients with lymph node metastasis and without lymph node metastasis;We evaluated the difference of sensitivity and specificity between serum miR-125b and CA125 combined with CA125 alone in diagnosing EOC.Meanwhile,120 newly diagnosed EOC patients with complete follow-up data were analyzed.Among them,47 patients received primary debulking surgery(PDS)and 73 patients received interval debulking surgery(IDS).Serum was collected 3 days before operation and 3～7 days after operation.Chemotherapy patients were treated with taxane platinum regimen,and all cases were treated with carboplatin5-6 area under curve(AUC)and paclitaxel 175 mg/m2 for six standard courses.RT-qPCR(real-time fluorescence quantitative detection)was used to analyze the changes of serum miR-125b level in patients with chemotherapy resistance and sensitivity before and after operation.Results :1.RT-qPCR analyses for serum miR-125b.The serum miR-125b levels in 42 healthy controls,40 benign tumors,35 borderline tumors,and 162 EOC were selected and assessed.The data showed that serum miR-125b levels were significantly lower in patients with EOC than those of others(P < 0.0001;Figure 1).No significant difference was showed between patients with benign tumors and borderline tumors with healthy controls(P > 0.05,respectively).2.miR-125b is a marker for predicting prognosis and diagnosis of EOC.RT-qPCR analysis showed that serum miR-125b levels were significantly lower in patients with high FIGO stage(III+IV)and lymph node metastasis than that in patients with low FIGO stage(I+II)(P < 0.001)and without lymph node metastasis(P = 0.032).However,there was no significant difference between patients with different ages,histological subtypes,tumor grade,distant metastasis,and CA125 levels,respectively(Table 1)(P > 0.05).3.Serum miR-125b levels with surgery or chemotherapy in patients with EOC.A statistically significant association was observed between preoperative and postoperative serum miR125b levels in patients with EOC(0.783 ± 0.174 vs 0.916 ±0.203,P = 0.003,Figure 2).A statistically significant difference of Serum miR-125b levels were also observed between the sensitive and resistant groups in patients with EOC(0.924 ± 0.186 vs 0.789 ± 0.1762,P < 0.0001,Figure 2).4.Combination of miR-125b with miR-125b as a tumor marker.The diagnostic efficiency of serum miR-125b and CA125 levels in distinguishing patients with EOC from patients without cancer were assessed.ROC curve analyses were performed to evaluate the predictive power of miR-125b for EOC and illustrated in Figure 3(a).The serum miR-125b levels could discriminate patients with EOC from other controls,with the sensitivity and specificity reached On the basis of the ROC curve,the cutoff value of CA125 was chosen as 35U/mL.By the cutoff value,CA125 displayed51.6% sensitivity and 89.6% specificity in diagnosis of EOC(Figure 3(b),P = 0.042).However,the combination of miR-125b with CA125 displayed 83.6% sensitivity and95.6% specificity(Figure 3(c),P < 0.001).Therefore,combining the miR-125b with CA125 could improve diagnostic sensitivity and specificity significantly.Conclusion1.Serum miR-125b levels were low in patients with EOC.Anti-cancer effect of Serum miR-125b.2.Low serum miR-125b levels were related to high FIGO stage and lymph node metastasis in patients with EOC.It is suggested that serum miR-125b may play an anti-cancer role.3.The level of EOC serum miR-125b before operation was lower than that of EOC serum miR-125b after operation.The level of EOC serum miR-125b in chemoresistant patients was lower than that in chemosensitive patients(P<0.0001).It indicates that the operation is effective and indicates whether the patient is sensitive to platinum drugs.Serum miR-125b may play an anti-tumor role.4.The Combination of serum miR-125b and serum CA125 could improve both sensitivity and specificity in diagnosis of EOC.