血清miR-155、miR-24对早期子宫内膜癌腹腔镜根治术后复发转移的预测价值

Predictive value of serum miR-155 and miR-24 for recurrence and metastasis after laparoscopic radical surgery for early endometrial cancer

目的 探讨血清微小核糖核酸-155 (miR-155)、微小核糖核酸-24 (miR-24)对早期子宫内膜癌(EC)腹腔镜根治术后复发转移的预测价值。方法 前瞻性选取2019年3月至2022年3月驻马店市第一人民医院收治的133例早期EC患者纳入研究,所有患者均接受腹腔镜根治术治疗,术后随访2年,脱落3例,根据是否发生复发转移分为复发转移组(n=21)和未复发转移组(n=109)。比较两组患者的基线资料及血清miR-155、miR-24表达水平,分析血清miR-155、miR-24与临床病理特征的关系,采用受试者工作特征(ROC)曲线评价血清miR-155、miR-24对术后复发转移的预测价值,以最佳截断值分析血清miR-155、miR-24与术后复发转移风险的关系及交互影响,并采用ROC曲线评价两者联合预测价值。结果 复发转移组患者的肿瘤直径及浆液性腺癌、临床分期Ⅱ期、病理分级G3级、肌层浸润深度≥1/2比例分别为(2.27±0.46) cm、33.33%、61.90%、47.62%、71.43%,明显大(高)于未复发转移组的(1.84±0.32) cm、5.50%、9.17%、22.02%、19.27%,差异均有统计学意义(P<0.05);复发转移组患者的血清miR-155表达水平为2.81±0.67,明显高于未复发转移组的2.26±0.39,miR-24表达水平为1.05±0.30,明显低于未复发转移组的1.64±0.52,差异均有统计学意义(P<0.05);列联相关系数分析结果显示,血清miR-155表达水平与肿瘤直径、浆液性腺癌、临床分期、病理分级、肌层浸润深度(r=0.612、0.637、0.703、0.685、0.711)均呈正相关,miR-24表达水平上述各项指标(r=-0.606、-0.641、-0.741、-0.698、-0.725)均呈负相关(P<0.05);ROC曲线分析结果显示,血清miR-155、miR-24预测术后复发转移的曲线下面积(AUC)分别为0.777 (95%CI:0.695~0.845)、0.759 (95%CI:0.676~0.829),联合预测的AUC为0.922 (95%CI:0.862~0.962),明显大于两者单独预测(Z=3.110、3.695,P均<0.001);危险度及交互作用分析结果显示,miR-155高表达与miR-24低表达同时存在所致术后复发转移风险的OR为80.400 (95%CI:9.408~687.106),γ=1.657,提示miR-155高表达与miR-24低表达在术后复发转移中呈正向交互作用(P<0.05)。结论 miR-155在早期EC术后复发转移患者血清中表达上调,miR-24表达下调,联合检测对术后复发转移具有较高预测价值,可作为临床预测术后复发转移的辅助指标,并有助于指导临床防治工作。

Objective To investigate the predictive value of serum micrornA-155(miR-155)and micrornA-24(miR-24)in the recurrence and metastasis of early endometrial cancer(EC)after laparoscopic radical surgery.Methods A prospective study was conducted on 133 patients with early EC who were admitted to Zhumadian First People's Hospital from March 2019 to March 2022.All patients underwent laparoscopic radical surgery.The patients were followed up for 2 years,and 3 patients were lost.According to whether there was recurrence and metastasis,the patients were divided into the recurrence and metastasis group(n=21)and the non-recurrence and non-metastasis group(n=109).Baseline data and serum miR-155 and miR-24 expression levels were compared between the two groups of patients.The relationship between serum miR-155,miR-24 and clinical pathological characteristics was analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum miR-155 and miR-24 for postoperative recurrence and metastasis.The relationship and interaction between serum miR-155,miR-24 and the risk of postoperative recurrence and metastasis were analyzed using optimal cutoff values.The predictive value of the combination of the two was evaluated using the ROC curve.Results The tumor diameter and proportions of patients with serous adenocarcinoma,clinical stageⅡ,pathological grade G3,and depth of muscular invasion≥1/2 in patients with recurrence and metastasis were (2.27±0.46) cm, 33.33%, 61.90%, 47.62%, and 71.43%, respectively, which were significantly larger (higher) than (1.84±0.32) cm, 5.50%, 9.17%, 22.02%, and 19.27% in patients without recurrence and metastasis (P<0.05). The expres-sion level of serum miR-155 in patients with recurrence and metastasis was 2.81±0.67, which was significantly higher than 2.26±0.39 in patients without recurrence and metastasis, and the expression level of miR-24 was 1.05±0.30, which was significantly lower than 1.64±0.52 in patients without recurrence and metastasis, with statistically significant differ-ences (P<0.05). Contingency coefficient analysis showed that the expression level of serum miR-155 was positively cor-related with tumor diameter, serous adenocarcinoma, clinical stage, pathological grade, and depth of muscular invasion (r=0.612, 0.637, 0.703, 0.685, 0.711), while the expression level of miR-24 was negatively correlated with all of the above indicators (r=-0.606, -0.641, -0.741, -0.698, -0.725), P<0.05. ROC curve analysis showed that the area under the curve (AUC) of serum miR-155 and miR-24 for predicting postoperative recurrence and metastasis were 0.777 (95%CI: 0.695-0.845) and 0.759 (95% CI: 0.676-0.829), respectively. The AUC of combined detection of serum miR-155 and miR-24 for prediction was 0.922 (95% CI: 0.862-0.962), which was significantly greater than that of the each index alone (Z=3.110, 3.695, both P<0.001). The analysis of risk and interaction showed that the OR of the risk of postoper-ative recurrence and metastasis caused by the coexistence of high expression of miR-155 and low expression of miR-24 was 80.400 (95%CI: 9.408-687.106), with γ=1.657, suggesting that there was a positive interaction between high expression of miR-155 and low expression of miR-24 in postoperative recurrence and metastasis (P<0.05). Conclusion miR-155 expression is up-regulated and miR-24 expression is down-regulated in the serum of patients with early recurrence and metastasis after laparoscopic radical surgery for early endometrial cancer. The combined detec-tion has high predictive value for postoperative recurrence and metastasis, and can be used as an auxiliary index for clini-cal prediction of postoperative recurrence and metastasis, and help to guide prevention and treatment.