Warning value of bioactive molecule expression in surgical specimens for early recurrence and metastasis of colorectal cancer after laparoscopic surgery
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摘要:目的
探讨联合检测手术标本中磷酸甘油酸变位酶1(PGAM1)、微小核糖核酸-433-3p(miR-433-3p)、细胞周期蛋白依赖性激酶1(CDK1)表达对结直肠癌(CRC)腹腔镜术后早期复发转移的预警价值。
方法回顾性分析120例CRC腹腔镜手术患者的临床资料, 根据术后1年复发转移发生情况分为发生组31例和未发生组89例。比较2组临床资料及手术标本中PGAM1、miR-433-3p、CDK1表达; 采用Logistic回归分析探讨PGAM1、miR-433-3p、CDK1对CRC腹腔镜术后复发转移的影响; 采用受试者工作特征(ROC)曲线分析PGAM1、miR-433-3p、CDK1单独及联合预测腹腔镜术后复发转移的价值,并进行外部验证。
结果发生组PGAM1 mRNA、CDK1 mRNA水平高于未发生组, miR-433-3p水平低于未发生组,差异有统计学意义(P < 0.05)。Logistic回归分析显示, PGAM1 mRNA(OR=1.387, 95%CI: 1.025~1.877)、miR-433-3p(OR=0.543, 95%CI: 0.319~0.924)、CDK1 mRNA(OR=1.353, 95%CI: 1.108~1.651)均是CRC腹腔镜术后复发转移的独立影响因素(P < 0.05)。ROC曲线分析显示, PGAM1 mRNA、miR-433-3p、CDK1 mRNA联合预测CRC腹腔镜术后复发转移的曲线下面积(AUC)为0.904(95%CI: 0.836~0.950), 优于各指标单独预测效能。个体值预测结果显示,诊断准确率为84.17%的条件下, CRC患者在腹腔镜术后会发生早期复发转移; 外部验证显示,联合预测结果与临床实际结果的Kappa值为0.864(95%CI: 0.611~0.984), 一致性较好。
结论手术标本中PGAM1、miR-433-3p、CDK1表达均是CRC患者腹腔镜术后早期复发转移的独立影响因素,联合检测对术后复发转移具有较高预测价值。
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关键词:
- 磷酸甘油酸变位酶1 /
- 微小RNA-433-3p /
- 细胞周期蛋白依赖性激酶1 /
- 结直肠癌 /
- 腹腔镜手术 /
- 复发 /
- 转移 /
- 预测价值
Abstract:ObjectiveTo explore the warning value of expression of phosphoglycerate mutase 1 (PGAM1), microRNA-433-3p (miR-433-3p) and cyclin-dependent kinase 1 (CDK1) in surgical specimens for early recurrence and metastasis after laparoscopic surgery for colorectal cancer (CRC).
MethodsClinical materials of 120 patients with laparoscopic surgery for CRC were retrospectively analyzed. Based on the incidence status of recurrence and metastasis within one year after surgery, the patients were divided into recurrence group (n=31) and non-recurrence group (n=89). The clinical materials and the expression levels of PGAM1, miR-433-3p, and CDK1 in surgical specimens were compared between the two groups. Logistic regression analysis was conducted to explore the impacts of PGAM1, miR-433-3p and CDK1 on recurrence and metastasis after laparoscopic surgery for CRC. Receiver operating characteristic (ROC) curve was drawn to analyze the values of PGAM1, miR-433-3p and CDK1 alone as well as their combination for predicting recurrence andmetastasis after laparoscopic surgery, and external validation was performed.
ResultsThe levels of PGAM1 mRNA and CDK1 mRNA in the recurrence group were significantly higher than those in the non-recurrence group, while the level of miR-433-3p was significantly lower (P < 0.05). Logistic regression analysis showed that PGAM1 mRNA (OR=1.387, 95%CI, 1.025 to 1.877), miR-433-3p (OR=0.543, 95%CI, 0.319 to 0.924), and CDK1 mRNA (OR=1.353, 95%CI, 1.108 to 1.651) were all independent factors associated with recurrence and metastasis after laparoscopic surgery for CRC (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) for the combined prediction of recurrence and metastasis after laparoscopic surgery for CRC by PGAM1 mRNA, miR-433-3p, and CDK1 mRNA was 0.904 (95%CI, 0.836 to 0.950), which was superior to the predictive performance of each indicator alone. Individual value prediction results indicated that CRC patients would experience early recurrence and metastasis after laparoscopic surgery under the condition of a diagnostic accuracy rate of 84.17%. External validation showed that the Kappa value between the combined prediction result and the actual clinical result was 0.864 (95%CI, 0.611 to 0.984), indicating good consistency.
ConclusionThe expression levels of PGAM1, miR-433-3p, and CDK1 in surgical specimens are all independent factors influencing early recurrence and metastasis after laparoscopic surgery for CRC patients, and their combined detection has high predictive value for postoperative recurrence and metastasis.
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表 1 2组临床资料比较(x±s)[n(%)]
临床资料 分类 发生组(n=31) 未发生组(n=89) t/χ2/U P 年龄/岁 65.82±8.00 63.97±10.14 0.920 0.359 性别 男 18(58.06) 55(61.80) 0.134 0.714 女 13(41.94) 34(38.20) 体质量指数/(kg/m2) 24.15±0.87 24.20±0.79 0.296 0.768 肿瘤位置 直肠 17(54.84) 53(59.55) 0.210 0.647 结肠 14(45.16) 36(40.45) 肿瘤最大直径/cm 5.94±1.50 5.59±1.74 0.998 0.321 T分期 T1期 1(3.22) 6(6.74) 0.075 0.784 T2+T3期 30(96.78) 83(93.26) N分期 N0期 1(3.22) 5(5.62) 0.002 0.962 N1+N2期 30(96.78) 84(94.38) 分化程度 低分化 6(19.35) 13(14.61) 0.512 0.609 中分化 14(45.16) 41(46.07) 高分化 11(35.49) 35(39.32) 肿瘤类型 隆起型 5(16.13) 10(11.23) 0.325 0.745 溃疡型 25(80.65) 77(86.52) 浸润型 1(3.22) 2(2.25) 组织学分型 腺癌 23(74.19) 66(74.16) 0.060 0.952 黏液腺癌 5(16.13) 17(19.10) 其他 3(9.68) 6(6.74) 表 2 2组手术标本PGAM1 mRNA、miR-433-3p、CDK1 mRNA比较(x±s)
组别 PGAM1 mRNA miR-433-3p CDK1 mRNA 发生组(n=31) 1.04±0.34** 0.43±0.14** 1.69±0.55** 未发生组(n=89) 0.75±0.21 0.68±0.22 0.91±0.30 PGAM1: 磷酸甘油酸变位酶1; CDK1: 细胞周期蛋白依赖性激酶1。
与未发生组比较, * * P < 0.01。表 3 联合预测模型的构建
变量 β S. E. Waldχ2 OR 95%CI P 下限 上限 PGAM1 mRNA(X1) 0.327 0.089 13.515 1.387 1.025 1.877 < 0.001 miR-433-3p(X2) -0.611 0.204 8.965 0.543 0.319 0.924 0.004 CDK1 mRNA(X3) 0.302 0.108 7.818 1.353 1.108 1.651 0.013 常数项 -0.835 0.243 11.801 0.434 — — < 0.001 表 4 联合预测因子及各协变量的预测参数
指标 AUC 95%CI cut-off值 敏感度/% 特异度/% P PGAM1 mRNA(X1) 0.777 0.692~0.848 0.77 77.42 69.66 < 0.001 miR-433-3p(X2) 0.754 0.667~0.828 0.46 67.74 71.91 < 0.001 CDK1 mRNA(X3) 0.758 0.671~0.831 1.32 80.65 64.04 < 0.001 联合预测因子 0.904 0.836~0.950 0.120 80.65 85.39 < 0.001 表 5 联合预测价值的验证
临床实际 联合预测 总计 一致性 χ2 P Kappa 95%CI 发生 未发生 发生 13 2 15 未发生 1 44 45 95.00% 40.248 < 0.001 0.864 0.611~0.984 总计 14 46 60 -
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