非小细胞肺癌组织中miR-605-5p、TNFAIP3表达水平及临床意义

The expression levels and clinical significance of miR-605-5p and TNFAIP3 in non-small cell lung cancer tissues

目的探讨非小细胞肺癌(NSCLC)组织中微小RNA-605-5p(miR-605-5p)、肿瘤坏死因子α诱导蛋白3(TNFAIP3)表达水平与患者5年内生存的关系。方法选取2014年2月—2018年1月在东南大学附属中大医院江北院区行手术切除的NSCLC患者87例,术中留取NSCLC组织及距其>3 cm的癌旁正常组织。免疫组织化学法检测NSCLC组织和癌旁正常组织TNFAIP3表达,实时荧光定量PCR法检测NSCLC组织和癌旁正常组织miR-605-5p、TNFAIP3 mRNA表达;术后随访5年,统计总生存率;比较生存组和死亡组NSCLC组织中miR-605-5p、TNFAIP3 mRNA表达水平;分析NSCLC组织中miR-605-5p、TNFAIP3 mRNA表达与临床病理特征的关系,miR-605-5p与TNFAIP3 mRNA表达水平的相关性,miR-605-5p、TNFAIP3 mRNA表达与患者生存的关系,影响NSCLC患者5年内生存的因素,miR-605-5p、TNFAIP3 mRNA表达水平对患者5年内生存的预测价值。结果NSCLC组织中TNFAIP3阳性率为25.29%,明显低于癌旁正常组织的57.47%(χ^(2)/P=18.575/<0.001);NSCLC组织中miR-605-5p表达水平明显高于癌旁正常组织,TNFAIP3 mRNA表达水平明显低于癌旁正常组织(t/P=16.316/<0.001、26.746/<0.001);miR-605-5p高表达组TNM分期中Ⅲ期、有淋巴结转移比例均明显高于miR-605-5p低表达组(χ^(2)/P=21.611/<0.001、6.472/<0.001);TNFAIP3 mRNA低表达组TNM分期中Ⅲ期、有淋巴结转移比例明显高于TNFAIP3 mRNA高表达组(χ^(2)/P=15.783/<0.001、13.839/<0.001);NSCLC组织中miR-605-5p与TNFAIP3 mRNA表达水平呈负相关(r/P=-0.453/<0.001);miR-605-5p低表达组5年总生存率为52.38%(22/42),明显高于miR-605-5p高表达组的26.67%(12/45),差异有统计学意义(χ^(2)/P=6.034/0.014);TNFAIP3 mRNA低表达组5年总生存率为21.95%(9/41),明显低于TNFAIP3 mRNA高表达组的54.35%(25/46),差异有统计学意义(χ^(2)/P=9.557/0.002);死亡组NSCLC组织中miR-605-5p表达水平明显高于生存组,TNFAIP3 mRNA表达水平明显低于生存组(t/P=2.515/0.014、6.678/<0.001);TNMⅢ期、有淋巴结转移、miR-605-5p高表达、TNFAIP3 mRNA低表达是影响NSCLC患者5年内生存的危险因素[OR(95%CI)=1.998(1.326~3.010)、2.845(1.577~5.132)、1.760(1.206~2.569)、2.534(1.618~3.969)];miR-605-5p、TNFAIP3 mRNA及二者联合预测患者5年内生存的AUC分别为0.761、0.837、0.910,二者联合的AUC高于各自单独预测的AUC(Z/P=2.716/0.007、1.986/0.047)。结论NSCLC组织中miR-605-5p高表达,TNFAIP3低表达,二者可能共同影响NSCLC患者5年内生存情况,对患者5年内生存具有较高预测价值。

Objective To investigate micro RNA-605-5p(miR-605-5p)and tumor necrosis factorαin non-small cell lung cancer(NSCLC)tissue and relationship between the expression level of inducible protein 3(TNFAIP3)and the 5-year survival of patients.Methods From February 2014 to January 2018,87 patients with NSCLC who underwent surgical resection in Jiangbei Hospital,Affiliated Zhongda Hospital of Southeast University were selected.During the operation,NSCLC tissue and normal tissue adjacent to the cancer were taken.Immunohistochemical method was used to detect the expression of TNFAIP3 in NSCLC tissue and normal tissue adjacent to cancer.Real time fluorescence quantitative PCR was used to detect the expression of miR-605-5p and TNFAIP3 mRNA in NSCLC tissue and normal tissue adjacent to cancer;Follow up for 5 years after surgery and calculate the overall survival rate;Compare the expression levels of miR-605-5p and TNFAIP3 mRNA in NSCLC tissues between the survival group and the death group;Analyze the relationship between miR-605-5p,TNFAIP3 mRNA expression and clinical pathological characteristics in NSCLC tissue,the correlation between miR-605-5p and TNFAIP3 mRNA expression levels,the relationship between miR-605-5p,TNFAIP3 mRNA expression and patient survival,factors affecting 5-year survival of NSCLC patients,and the predictive value of miR-605-5p,TNFAIP3 mRNA expression levels on 5-year survival of patients.Results The positive rate of TNFAIP3 in NSCLC tissue was 25.29%,significantly lower than 57.47%in normal tissues adjacent to cancer(χ^(2)/P=18.575/<0.001);The expression level of miR-605-5p in NSCLC tissue was significantly higher than that in normal tissue adjacent to cancer,while the expression level of TNFAIP3 mRNA was significantly lower than that in normal tissue adjacent to cancer(t/P=16.316/<0.001,26.746/<0.001);The proportion of stage III and lymph node metastasis in TNM staging in the high expression group of miR-605-5p was significantly higher than that in the low expression group of miR-605-5p(χ^(2)/P=21.611/<0.001,6.472/<0.001);The proportion of stage III and lymph node metastasis in TNM staging was significantly higher in the low expression group of TNFAIP3 mRNA than in the high expression group of TNFAIP3 mRNA(χ^(2)/P=15.783/<0.001,13.839/<0.001);There is a negative correlation between miR-605-5p and TNFAIP3 mRNA expression level in NSCLC tissue(r/P=-0.453/<0.001);The 5-year overall survival rate of the miR-605-5p low expression group was 52.38%(22/42),significantly higher than the 26.67%(12/45)of the miR-605-5p high expression group,and the difference was statistically significant(χ^(2)/P=6.034/0.014);The 5-year overall survival rate of the low expression group of TNFAIP3 mRNA was 21.95%(9/41),significantly lower than 54.35%(25/46)of the high expression group of TNFAIP3 mRNA,and the difference was statistically significant(χ^(2)/P=9.557/0.002);The expression level of miR-605-5p in NSCLC tissue of the death group was significantly higher than that of the survival group,while the expression level of TNFAIP3 mRNA was significantly lower than that of the survival group(t/P=2.515/0.014,6.678/<0.001);TNM stage III,lymph node metastasis,high expression of miR-605-5p,and low expression of TNFAIP3 mRNA are risk factors affecting 5-year survival in NSCLC patients[OR(95%CI)=1.998(1.326-3.010),2.845(1.577-5.132),1.760(1.206-2.569),2.534(1.618-3.969)];The AUC predicted by miR-605-5p,TNFAIP3 mRNA,and their combination for 5-year survival in patients were 0.761,0.837,and 0.910,respectively.The combined AUC of miR-605-5p and TNFAIP3 mRNA was higher than the AUC predicted by miR-605-5p and TNFAIP3 mRNA alone(Z/P=2.716/0.007,1.986/0.047).Conclusion High expression of miR-605-5p and low expression of TNFAIP3 in NSCLC tissue may jointly affect the 5-year survival of NSCLC patients,which has high predictive value for 5-year survival.