非小细胞肺癌组织中lncRNA FOXD2-AS1、miR-1913表达与患者生存期的关系

Relationship between the expression of lncRNA FOXD2-AS1 and miR-1913 in non-small cell lung cancer tissue and survival period

目的探究非小细胞肺癌(NSCLC)组织中长链非编码RNA(lncRNA)FOXD2-AS1、miR-1913的表达与患者生存期的关系。方法选取2017年11月—2019年11月滨州医学院烟台附属医院肿瘤中心收治的NSCLC患者100例癌组织和癌旁组织作为研究对象。根据术后3年预后情况分为生存组58例和死亡组42例,采用实时荧光定量—聚合酶链式反应(qRT-PCR)测定组织中lncRNA FOXD2-AS1、miR-1913表达水平;Pearson法分析NSCLC组织中lncRNA FOXD2-AS1与miR-1913表达水平的相关性;用Kaplan-Meier法分析NSCLC组织中lncRNA FOXD2-AS1、miR-1913表达与预后的关系;Cox分析NSCLC患者预后的影响因素。结果与癌旁组织比较,NSCLC组织中lncRNA FOXD2-AS1表达水平升高,miR-1913表达水平降低(t/P=11.439/<0.001、17.709/<0.001);Target Scan Human网址预测lncRNA FOXD2-AS1与miR-1913间存在结合位点;NSCLC组织中lncRNA FOXD2-AS1与miR-1913表达水平呈负相关(r=-0.406,P<0.001);与生存组比较,死亡组患者癌组织中lncRNA FOXD2-AS1表达水平升高,miR-1913表达水平降低(t/P=6.973/<0.001、6.307/<0.001);TNM分期为Ⅲ+Ⅳ期、发生淋巴结转移、低分化程度的NSCLC患者癌组织lncRNA FOXD2-AS1高表达比例高于TNM分期为Ⅰ+Ⅱ期、未发生淋巴结转移、中/高分化程度的NSCLC患者(χ^(2)/P=5.962/0.015、5.104/0.024、6.150/0.013),而miR-1913低表达比例高于TNM分期为Ⅰ+Ⅱ期、未发生淋巴结转移、中/高分化程度的NSCLC患者(χ^(2)/P=11.457/0.001、7.695/0.006、11.349/0.001);lncRNA FOXD2-AS1高表达NSCLC患者3年生存率低于lncRNA FOXD2-AS1低表达患者,miR-1913高表达患者3年生存率高于miR-1913低表达NSCLC患者(χ^(2)/P=7.830/0.005、6.125/0.013);多因素Cox分析显示,miR-1913高是NSCLC患者预后的保护因素[OR(95%CI)=0.864(0.774~0.964)],lncRNA FOXD2-AS1高、TNMⅢ+Ⅳ期、有淋巴结转移、分化程度低是NSCLC患者预后的危险因素[OR(95%CI)=2.544(1.481~4.370)、3.647(1.614~8.242)、2.544(1.481~4.370)、2.986(1.361~6.553)]。结论NSCLC组织中lncRNA FOXD2-AS1表达水平升高,miR-1913的表达水平降低,两者与患者预后生存期有关。

Objective To investigate the relationship between the expression of long coding RNA FOXD2 adjacent opposite strand RNA 1(lncRNA FOXD2-AS1)and miR-1913 in non-small cell lung cancer(NSCLC)tissue and survival period.Methods A total of 100 NSCLC patients admitted to Binzhou Medical College Yantai Affiliated Hospital Cancer Center from November 2017 to November 2019 were regarded as the study subjects.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was applied to determine the expression levels of lncRNA FOXD2-AS1 and miR-1913 in tissues;Pearson method was applied to analyze the correlation between lncRNA FOXD2-AS1 and miR-1913 expression levels in NSCLC tissues;Kaplan-Meier method was applied to analyze the relationship between lncRNA FOXD2-AS1,miR-1913 expression and prognosis in NSCLC tissues;Cox was applied to analyze the influencing factors of prognosis in NSCLC patients.Results Compared with the adjacent tissues,the expression level of lncRNA FOXD2-AS1 in NSCLC tissues increased and the expression level of miR-1913 decreased(t=11.439,17.709,P<0.001).Target Scan Human website predicts that there is a binding site between lncRNA FOXD2-AS1 and miR-1913.The expression level of lncRNA FOXD2-AS1 in NSCLC was negatively correlated with miR-1913(r=-0.406,P<0.001).Compared with the survival subgroup,the expression level of lncRNA FOXD2-AS1 in the death subgroup increased and the expression level of miR-1913 decreased(t=6.973,6.307,P<0.001).The high expression rate of lncRNA FOXD2-AS1 in NSCLC patients with TNM stageⅢ+Ⅳ,lymph node metastasis and low differentiation was higher than that in NSCLC patients with TNM stageⅠ+Ⅱ(χ^(2)=5.962,P=0.015),no lymph node metastasis(χ^(2)=5.104,P=0.024)and moderate/high differentiation(χ^(2)=6.150,P=0.013).The low expression rate of miR-1913 in NSCLC patients with TNM stageⅢ+Ⅳ,lymph node metastasis and low differentiation was higher than that in NSCLC patients with TNM stageⅠ+Ⅱ(χ^(2)=11.457,P=0.001),no lymph node metastasis(χ^(2)=7.695,P=0.006)and moderate/high differentiation(χ^(2)=11.349,P=0.001).The 3-year survival rate of NSCLC patients with high expression of lncRNA FOXD2-AS1 was lower than that of patients with low expression of lncRNA FOXD2-AS1(χ^(2)=7.830,P=0.005),and that of patients with high expression of miR-1913 was higher than that of patients with low expression of miR-1913(χ^(2)=6.125,P=0.013).Multivariate Cox analysis showed that high miR-1913 was a protective factor for the prognosis of NSCLC patients,the high level of lncRNA FOXD2-AS1,TNMⅢ+Ⅳstage,lymph node metastasis and low degree of differentiation are the risk factors for the prognosis of NSCLC patients[OR(95%CI)=0.864(0.774-0.964),2.544(1.481-4.370),3.647(1.614-8.242),2.544(1.481-4.370),2.986(1.361-6.553)].Conclusion The expression level of lncRNA FOXD2-AS1 increases and the expression level of miR-1913 decreases in NSCLC tissue,both of which are related to the prognostic survival period of patients.