Value of serum microRNA-184 and microRNA-451a expression in predicting recurrent metastasis after radical surgery of patients with non-small cell lung cancer in stage Ⅰ to ⅡA
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摘要:目的
探讨血清微小核糖核酸(miRNA)-184、miR-451a表达对Ⅰ~ⅡA期非小细胞肺癌(NSCLC)根治术后复发转移的预测价值。
方法选取2020年1月—2021年10月在本院行根治性切除术的203例Ⅰ~ⅡA期NSCLC患者为NSCLC组, 随访2年根据复发转移情况分为复发转移组30例和无复发转移组173例; 另选取同期87名体检健康志愿者为对照组。采用实时荧光定量聚合酶链式反应检测血清miR-184、miR-451a表达。采用多因素Logistic回归模型分析影响Ⅰ~ⅡA期NSCLC根治术后复发转移的因素; 采用受试者工作特征(ROC)曲线分析血清miR-184、miR-451a表达对复发转移的预测价值。
结果与对照组比较, NSCLC组血清miR-184、miR-451a表达降低，差异有统计学意义(P < 0.05)。随访2年，203例Ⅰ~ⅡA期NSCLC患者术后复发转移率为14.78%(30/203)。与无复发转移组比较，复发转移组血清miR-184、miR-451a表达降低，差异有统计学意义(P < 0.05)。Ⅰ~ⅡA期NSCLC根治术后复发转移的独立危险因素为ⅡA期、低分化、术后辅助化疗，独立保护因素为miR-184升高、miR-451a升高(P < 0.05)。血清miR-184、miR-451a表达联合预测Ⅰ~ⅡA期NSCLC根治术后复发转移的曲线下面积为0.868, 大于血清miR-184、miR-451a表达单独预测的0.784、0.781, 差异有统计学意义(P < 0.05)。
结论Ⅰ~ⅡA期NSCLC患者血清miR-184、miR-451a呈低表达，与根治术后复发转移密切相关，血清miR-184、miR-451a联合检测对Ⅰ~ⅡA期NSCLC根治术后复发转移有较高的预测价值。
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关键词:
- 非小细胞肺癌 /
- 根治性切除术 /
- 微小核糖核酸-184 /
- 微小核糖核酸-451a /
- 复发转移
Abstract:ObjectiveTo investigate the value of serum microRNA (miRNA)-184 and miR-451a expression in predicting recurrent metastasis after radical resection of stage Ⅰ to ⅡA non-small cell lung cancer (NSCLC).
MethodsA total of 203 patients with radical resection of stage Ⅰ to ⅡA NSCLC in the hospital from January 2020 to October 2021 were selected as NSCLC group. According to the recurrence and metastasis status during the 2-year follow-up, they were divided into recurrence and metastasis group with 30 cases and non-recurrence and metastasis group with 173 cases. Additionally, 87 healthy volunteers with physical examinations in the same period were selected as control group. Real-time quantitative polymerase chain reaction was used to detect serum expression of miR-184 and miR-451a. Multivariate Logistic regression model was used to analyze the factors affecting recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC. Receiver operating characteristic (ROC) curve was used to analyze the value of serum miR-184 and miR-451a expression in predicting recurrence and metastasis.
ResultsCompared with the control group, the expression of serum miR-184 and miR-451a in the NSCLC group decreased significantly (P < 0.05). After 2 years of follow-up, the recurrence and metastasis rate of 203 patients with stage Ⅰ to ⅡA NSCLC was 14.78% (30/203). Compared with the non-recurrence and metastasis group, the expression of serum miR-184 and miR-451a in the recurrence and metastasis group decreased significantly (P < 0.05). The independent risk factors for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC were stage ⅡA, poor differentiation and postoperative adjuvant chemotherapy, while the independent protective factors were increased miR-184 and miR-451a expression (P < 0.05). The area under the curve (AUC) of the combined prediction of serum miR-184 and miR-451a expression for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC was 0.868, which was greater than 0.784 and 0.781 of serum miR-184 and miR-451a expression alone (P < 0.05).
ConclusionThe serum miR-184 and miR-451a expression in patients with stage Ⅰ to ⅡA NSCLC is low and closely related to recurrence and metastasis after radical resection. The combined detection of serum miR-184 and miR-451a has a high predictive value for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC.
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表 1 NSCLC组与对照组血清miR-184、miR-451a表达水平比较(x±s)
组别 n miR-184 miR-451a NSCLC组 203 0.67±0.15* 0.54±0.11* 对照组 87 1.21±0.30 1.13±0.24 与对照组比较, * P < 0.05。 
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表 2 单因素分析结果(x±s)[n(%)]
变量 分类 复发转移组(n=30) 无复发转移组(n=173) χ2/t/Z P 性别 男 21(70.00) 103(59.54) 1.177 0.278 女 9(30.00) 70(40.46) 平均年龄/岁 62.53±8.16 58.61±7.71 2.553 0.011 年龄分布 >60岁 18(60.00) 82(47.40) 1.624 0.203 ≤60岁 12(40.00) 91(52.60) 吸烟 有 18(60.00) 98(56.65) 0.117 0.732 无 12(40.00) 75(43.35) 病理类型 腺癌 23(76.67) 118(68.21) 1.085 0.781 鳞癌 4(13.33) 26(15.03) 大细胞癌 2(6.67) 21(12.14) 其他 1(3.33) 8(4.62) TNM分期 ⅠA期 2(6.67) 134(77.46) -8.173 < 0.001 ⅠB期 8(26.67) 24(13.87) ⅡA期 20(66.67) 15(8.67) 肿瘤原发部位 左肺上叶 8(26.67) 35(20.23) 1.533 0.821 左肺下叶 6(20.00) 27(15.61) 右肺上叶 9(30.00) 70(40.46) 右肺中叶 2(6.67) 11(6.36) 右肺下叶 5(16.67) 30(17.34) 肿瘤直径 >3 cm 6(20.00) 21(12.14) 0.773 0.379 ≤3 cm 24(80.00) 152(87.86) 分化程度 低分化 7(23.33) 11(6.36) 7.137 0.008 中高分化 23(76.67) 162(93.64) 手术方式 全肺切除 5(16.67) 12(6.94) 2.014 0.156 肺叶切除 25(83.33) 161(93.06) 术后辅助化疗 是 15(50.00) 20(11.56) 26.475 < 0.001 否 15(50.00) 153(88.44) miR-184 0.54±0.12 0.69±0.14 -5.454 < 0.001 miR-451a 0.44±0.09 0.55±0.11 -5.340 < 0.001
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表 3 多因素Logistic回归分析结果
变量 赋值 β SE Wald χ2 P OR 95%CI 年龄 原值录入 0.041 0.038 1.136 0.284 1.042 0.966~1.123 TNM分期 ⅠA期=1 — — 15.605 <0.001 — — ⅠB期=2 1.223 0.734 2.778 0.096 3.397 0.806~14.308 ⅡA期=3 1.599 0.551 8.438 0.004 4.950 1.682~14.565 分化程度 低分化=1, 中高分化=0 1.025 0.464 4.869 0.027 2.786 1.121~6.924 术后辅助化疗 是=1, 否=0 1.208 0.593 4.152 0.042 3.348 1.047~10.705 miR-184 原值录入 -0.085 0.020 18.658 <0.001 0.918 0.884~0.955 miR-451a 原值录入 -0.118 0.027 18.769 <0.001 0.889 0.842~0.937
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表 4 血清miR-184、miR-451a对Ⅰ~ⅡA期NSCLC根治术后复发转移的预测价值
因素 AUC 95%CI 最佳截断值 敏感度/% 特异度/% 最大约登指数 miR-184 0.784 0.721~0.839 0.69 100.00 49.13 0.491 miR-451a 0.781 0.718~0.836 0.52 80.00 61.27 0.413 二项联合 0.868 0.814~0.912 — 93.33 66.47 0.598
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