Predictive Role Of CA125 In Chemotherapy Resistance Of Advanced High-grade Serous Ovarian Cancer

Objective:To investigate the predictive effect of serum initial CA125 level on chemotherapy resistance of advanced high-grade Serous Ovarian Cancer(HGSOC).Methods:193 patients with advanced(stage III-IV)high-grade serous ovarian cancer in the Affiliated Hospital of Qingdao University from January 2003 to January 2019 were retrospectively analyzed.The subjects included age,serum initial CA125 level,ascites before treatment,intraoperative tumor size,postoperative pathological stage and immunohistochemical results,chemotherapy resistance,and progression-free survival of patients and other clinical data.The initial serum CA125 cut-off value(optimal cut-off value)was obtained by analyzing the ROC curve(receiver operating characteristic curve),and the group with high CA125 level and low CA125 level were divided according to the cut-off value.The expression of genes related to chemotherapy resistance was further compared between the two groups,and the differences in chemotherapy resistance and progression-free survival between the two groups were analyzed.Meanwhile,the expression of HMGB1 related to tumor invasion and metastasis in normal ovarian group,low CA125 group and high CA125 group was detected by immunohistochemical method.Results: 1.The ROC curve was analyzed and calculated according to the correct index(calculation method:The maximum sensitivity + specificity-1)method calculated the Cut-off value(optimal cut-off value)of serum CA125 level before treatment to predict chemotherapy sensitivity and drug resistance in patients with advanced HGSOC was703.85U/ m L,the area under the curve(AUC)was 0.656,the sensitivity was 65.5%,the specificity was 75.7%,and the P value was 0.004.With a 95% confidence interval of0.569-0.742,subjects were divided into two groups: low CA125 level group and high CA125 level group.Low CA125 level group was defined as patients whose initial serum CA125 value was less than 703.85U/ m L.Patients with a high CA125 level were defined as those with an initial serum CA125 level higher than 703.85U/ m L.2.The mean age of patients in the low CA125 group was(57.81±10.17)years old,and the mean age of patients in the high CA125 group was(56.89±8.70)years old.There was no statistically significant difference in age between the two groups(p>0.05).3.The longest diameter of ovarian tumor before treatment was(83.30±44.69)mm in the low CA125 group,(80.25±39.65)mm in the high CA125 group,and(36.63±31.58)mm in the low CA125 group.The group with high CA125 level was about(42.58±34.29)mm.Statisically,there was no significant difference in the longest diameter of ovarian tumor and the depth of ascites before treatment between the two groups(p>0.05).4.The chemotherapy resistance rate of the low CA125 group was 65.88%,which was significantly higher than that of the high CA125 group(32.41%)(p<0.05);The progression-free survival(PFS)of patients with low CA125 level was(7.92±4.80)months,and that of patients with high CA125 level was(9.82±5.55)months,which was significantly different(p<0.05).5.The positive expression rates of mutant P53,ER,P16 and PAX-8 in low CA125 level group were 79.17%,82.54%,95.65% and 93.75%,respectively,which were significantly higher than those in high CA125 level group(p<0.05),and the positive rate of PR was37.14%,which was significantly lower than that of high CA125 group 54.17%(p<0.05).6.The HMGB1 positive cell rate in the normal ovarian group(0.12% ± 0.02)was significantly lower than that in the HGSOC patients(17.80%±4.12)(p<0.05).The HMGB1 positive cell density in the normal ovary group(0.10±0.08)was significantly lower than that in the HGSOC patients(2.70±1.81)(p<0.05).7.The percentage of HMGB1 positive cells in low CA125 level group(28.32%±13.63)was significantly higher than that in high CA125 level group(9.21%±2.02).The HMGB1 positive cell density of low CA125 level group(4.06±2.37)was significantly higher than that of high CA125 level group(2.09±1.83)(p<0.05).Conclusions: 1.The expression levels of drug-resistant genes,such as mutant P53,ER,P16 and PAX-8,were significantly increased in low CA125 group,while the expression levels of PR gene were decreased.2.The HMGB1 protein associated with tumor invasion and metastasis was composed of high expression level at low CA125 level;3.Patients with advanced high-grade serous ovarian cancer with low initial CA125 level were more likely to develop chemotherapy resistance,with shorter progression-free survival and worse prognosis.