摘要
目的 旨在分析非小细胞肺癌(NSCLC)患者血清miR-550a-5p、中性粒细胞与淋巴细胞比值(NLR)、血小板计数与淋巴细胞比值(PLR)和系统性免疫性炎性指数(SII)水平变化,并探讨各指标联合对NSCLC患者脊柱转移发生的诊断价值.方法 收集2018年1月至2023年至1月于承德医学院附属医院脊柱外科住院治疗的154例NSCLC患者.根据全身骨显像检查结果,发生脊柱转移者65例(转移组),未发生脊柱转移者89例(无转移组).收集所有患者的一般资料.采用反转录定量聚合酶链反应(RT-qPCR)检测外周血miR-550a-5p水平.采用受试者工作特征曲线分析各指标对脊柱转移发生的诊断价值.采用多因素logistic回归分析确定与乳腺癌发生的独立危险因素.使用R程序建立列线图预测模型,并对模型的预测准确性及区分度进行验证.结果 与无转移组相比,转移组患者血清miR-550a-5p、NLR、PLR和SⅡ水平明显升高(P<0.05).与肺鳞癌、Ⅰ-Ⅱ期患者相比,肺腺癌、Ⅲ-Ⅳ期的脊柱转移组患者血清miR-550a-5p水平明显升高(P<0.05).miR-550a-5p、CEA、CYFRA21-1、NLR、PLR和 SⅡ诊断NSCLC 患者脊柱发生的 AUC分别为 0.943、0.825、0.767、0.700、0.661、0.833.miR-550a-5p诊断NSCLC脊柱转移的效能高于 CEA(P=0.003)、CYFRA21-1(P<0.001)、NLR(P<0.001)、PLR(P<0.001)和 SII(P<0.001).多因素回归分析显示,miR-550a-5p(OR=8.506)、NLR(OR=2.976)和 SⅡ(OR=1.013)均是 NSCLC 患者脊柱转移发生的危险因素(P<0.05).miR-550a-5p、NLR和SII联合的AUC为0.985(0.952~0.998);当最佳截断值为0.928时,敏感度为98.46%,特异度为94.38%.基于血清miR-550a-5p、NLR和SII构建列线图预测模型具有良好的预测准确性(AUC=0.992)和一致性(C-index=0.992).Hosmer-Lemeshow拟合优度检验表明模型具有较好的校准度(P=0.739).结论 血清miR-550a-5p与NLR、SII联合应用可以提高NSCLC脊柱转移的临床诊断效能,具有作为NSCLC患者脊柱转移辅助筛查生物标志物的应用前景.
Abstract
Objective To analyze the changes in the levels of serum miR-550a-5p,neutrophil-to-lymphocyte ratio(NLR),plate-let count-to-lymphocyte ratio(PLR),and systemic immune inflamma-tory index(SII)in patients with non-small-cell lung cancer(NSCLC),and to explore the diagnostic value of the combination of these indicators for the occurrence of spinal metastasis in NSCLC pa-tients.Methods 154 NSCLC patients hospitalized in the Spinal Surgery Department of Chengde Medical College Affiliated Hospital from January 2018 to January 2023 were included.The whole-body bone imaging showed that 65 cases of spinal metastasis(metastasis group)and 89 cases of spinal metastasis(no metastasis group).General information of all patients was collected.Peripheral blood miR-550a-5p levels were detected by reverse transcription quantita-tive polymerase chain reaction(RT-qPCR).The diagnostic value of each indicator for the occurrence of spinal metastasis was analyzed by using the working characteristic curve of the subjects.Multivariate logistic regression analysis was used to determine the indepen-dent risk factors associated with the occurrence of breast cancer.A nomogram prediction model was developed using the R program,and the predictive accuracy and discrimination of the model were validated.Results Serum miR-550a-5p,NLR,PLR and SⅡ levels were significantly higher in patients in the metastasis group compared with those of the no-metastasis group(P<0.05).Serum miR-550a-5p levels were significantly higher in patients with lung adenocarcinoma and stage Ⅲ-Ⅳ spinal metastasis group compared with patients with squamous lung cancer and stage Ⅰ-Ⅱ(P<0.05).The AUCs of miR-550a-5p,CEA,CYFRA21-1,NLR,PLR and SⅡ for diagnosing spinal development in NSCLC patients were 0.943,0.825,0.767,0.700,0.661,and 0.833,respectively.miR-550a-5p was more efficacious in diagnosing spinal metastasis in NSCLC than CEA(Z=3.003,P=0.003),CYFRA21-1(Z=3.718,P<0.001),NLR(Z=4.972,P<0.001),PLR(Z=5.724,P<0.001)and SII(Z=2.908,P<0.001).Multivariate regression analysis showed that miR-550a-5p(OR=8.506),NLR(OR=2.976)and SII(OR=1.013)were independent risk factors for the occurrence of spinal metastasis in NSCLC patients(P<0.05).The AUC of the combination of miR-550a-5p,NLR and SII was 0.985(0.952-0.998);when the optimal cut-off value was 0.928,the sensitivity was 98.46%and the specificity was 94.38%.Constructing a nomogram prediction model based on serum miR-550a-5p,NLR and SII had good predictive accuracy(AUC=0.992)and consistency(C-index=0.992).The Hosmer-Leme-show goodness-of-fit test showed that the model had good calibration(P=0.739).Conclusion Serum miR-550a-5p in combination with NLR and SII can improve the clinical diagnostic efficacy of NSCLC spinal metastasis,and has a promising application as an ad-junctive screening biomarker for spinal metastasis in NSCLC patients.
基金项目
河北省卫生健康委2024年政府资助临床医学优秀人才培养项目(ZF2024236)