新疆医科大学学报

目的 探讨血清微小核糖核酸(microRNA,miRNA)谱与临床病理因子联合应用对晚期上皮性卵巢癌患者预后评估的临床效能。方法 选取2016年4月至2020年4月在本院确诊且接受手术治疗的上皮性卵巢癌患者共284例作为卵巢癌组，另纳入同期在本院妇科就诊并确诊为卵巢良性肿瘤患者共97例作为良性对照组。从每组中各选取30例患者的血清样本，采用TaqMan低密度微阵列芯片技术测定两组血清miRNA表达是否存在明显差异，并确定目标miRNA。之后应用血清miRNA试剂盒测定所有研究对象血清中目标miRNA表达，统计分析卵巢癌组和良性对照组患者目标miRNA的表达差异。对纳入的卵巢癌患者进行为期5年的随访工作，根据患者5年内预后情况建立亚组，分别为预后良好组(n=186)和预后不佳组(n=98),分析其与卵巢癌患者的生存预后及相关临床病理学特征之间的关系。采用受试者工作特征曲线(ROC)分析血清miRNA联合检测对上皮性卵巢癌患者5年内生存预后的预测效能。采用多因素Cox回归分析影响上皮性卵巢癌患者预后不佳的危险因素。结果 通过TaqMan低密度微阵列芯片最终选中并验证miR-21、miR-485、miR-128在两组患者血清中的表达差异有统计学意义，进一步检测显示，与良性对照组相比，卵巢癌组血清中miR-21相对表达量升高，而miR-485和miR-128相对表达量降低(P<0.05);不同病灶最大直径、分化程度、FIGO分期及CA125水平的卵巢癌患者间，血清miR-21、miR-485、miR-128的表达水平差异均有统计学意义(P<0.05);与预后不佳组相比，预后良好组血清miR-21相对表达量降低，而miR-485和miR-128相对表达量升高(P<0.05);miR-21、miR-485、miR-128单独检测均具有一定的预测效能，而3项指标联合检测的预测效能更高，其曲线下面积(AUC)为0.923(95%CI:0.891～0.949);FIGO分期、淋巴结转移、腹膜转移、miR-21>1.30、miR-485<1.05、miR-128>2.17是影响上皮性卵巢癌患者预后不良的独立危险因素(P<0.05)。结论 血清miR-21、miR-485、miR-128在预测卵巢癌患者5年内生存预后方面的效能较好，上述3项指标联合检测在评估卵巢癌患者5年内生存预后方面的效能更高，提示针对晚期上皮性卵巢癌患者进行相关指标的测定，对精准评估患者预后并针对性优化诊疗方案具有较好的临床意义。

Objective To investigate the clinical efficacy of combining serum microRNA(miRNA) profileswith clinicopathological factors for prognostic assessment in patients with advanced epithelial ovarian cancer. Methods A total of 284 patients with epithelial ovarian cancer who were diagnosed and underwent surgical treatment in the hospital from April 2016 to April 2020 were selected as the ovarian cancer group, and a total of 97 patients diagnosed with benign ovarian tumors who visited in the hospital during the same period were included as the benign control group. Serum samples from 30 patients in each group were selected to determine whether there were significant differences in serum miRNA expression between the 2 groups using TaqMan low-density microarray technology, and to identify target miRNAs. Subsequently, serum miRNA kits were used to measure the expression of target miRNAs in the serum of all study subjects, and the differences in target miRNA expression between the ovarian cancer group and the benign control group were statistically analyzed. The included ovarian cancer patients were followed up for 5 years.Based on the prognosis within 5 years, subgroups were established, they were divided into subgroups: a good prognosis group(n=186) and a poor prognosis group(n=98). The relationship between target miRNA expression and survival prognosis as well as related clinicopathological characteristics in ovarian cancer patients was analyzed.Receiver operating characteristic curve(ROC curve) was used to evaluate the predictive efficacy of combined serum miRNA detection for the 5-year survival prognosis of patients with epithelial ovarian cancer. Multivariate Cox regression analysis was employed to identify risk factors influencing poor prognosis in patients with epithelial ovarian cancer. Results The TaqMan low-density microarray chip finally selected and verified that there were significant differences in the expression of miR-21, miR-485,and miR-128 in the serum of the 2 groups of the patients. Further detection showed that, compared with the benign control group, the relative expression levels of serum miR-21 were elevated in the ovarian cancer group, while the relative expression levels of miR-485 and miR-128 were decreased(P<0.05). There were statistically significant differences in serum miR-21, miR-485, and miR-128 expression levels among ovarian cancer with different maximum lesion diameters, degrees of differentiation, FIGO stages, and CA125 levels(P<0.05). Compared with the poor prognosis group, the relative expression levels of serum miR-21 were lower in the good prognosis group, while the relative expression levels of miR-485 and miR-128 were higher(P<0.05). The individual detection of miR-21, miR-485, and miR-128 all had certain predictive efficacy, whereas the combined detection of the 3 indicators showed higher predictive efficacy, with an area under the curve(AUC) of 0.923(95%CI: 0.891～0.949). FIGO stage, lymph node metastasis, peritoneal metastasis, miR-21>1.30, miR-485<1.05, and miR-128>2.17 were independent risk factors for poor prognosis in patients with epithelial ovarian cancer(P<0.05). Conclusion Serum miR-21, miR-485, and miR-128 show good performance in predicting the 5-year survival prognosis of ovarian cancer patients, and the combined detection of these 3 indicators demonstrates even higher efficacy in evaluating the 5-year survival prognosis. This suggests that measuring these indicators in patients with advanced epithelial ovarian cancer has significant clinical value for the precise assessment of prognosis and the targeted optimization of diagnosis and treatment plans.