Quantitative Relationship Between HOTAIR And Invasion And Lymph Node Metastasis In Non-small Cell Lung Cancer

Objective:To study the quantitative relationship between the expression levels of HOTAIR mRNA and the invasiveness and lymphatic metastasis of non-small cell lung cancer(NSCLC),and evaluate its value in predicting the invasiveness and lymphatic metastasis,and explore the potential mechanism associated with its enhancement for the invasiveness and lymphatic metastasis.Methods:A total of 237 NSCLC patients were chosen,who underwent tumor resection and were definitely diagnosed with histopathological examination.Tumor tissue and adjacent tissue were collected and then detected for the relative expression of HOTAIR mRNA with RT-qPCR,and VEGF,MMP-7 and MMP-9 were also detected for their mRNA expression in tumor tissue.NSCLC patients with invasiveness(invasive carcinoma)or lymphatic metastasis were defined as case group,and NSCLC patients without invasiveness(superificial carcinoma)or lymphatic metastasis as control group.The relative expression of HOTAIR mRNA were graded into four grades(Grade 1:≤QI,Grade 2:>Q1 and ≤:Q2,Grade3:>Q2 and ≤Q3,and Grade 4:>Q3)according to Q1,Q2 and Q3 of HOTAIR mRNA of control group.Multivariate analysis was performed to determine odds ratios(ORs)between HOTAIR expression level and the invasiveness and metastasis of NSCLC using Logistic regression,and ROC curves and diagnostic test were used in evaluating the value of HOTAIR expression level applied in predicting the invasiveness and lymphatic metastasis of NSCLC.In addition,the relative expression of VEGF,MMP-7 and MMP-9 mRNA were compared between the case group and control group.Results:(1)The relative expression level of HOTAIR mRNA was higher in tumor tissue than in adjacent tissue;②The relative expression of HOTAIR mRNA>Q2(4.56)was an independent risk factor of invasive earcinoma,and the adjusted of grade 3[>Q2(4.56)and ≤Q3(11.59)]and grade 4[>Q3(11.59)]were 4.016 and 22.959,respectively;③The value of grade 4 applied in predicting the invasiveness of NSCLC was up to moderate with the area under curves(AUC)of 0.786(SE:0.025,P<0.001);④The relative expression of HOTAIR mRNA>Q2(5.32)was an independent risk factor of the metastasis of NSCLC,and the adjusted ORs of grade 3[>Q2(5.32)and ≤Q3(11.11)]and grade 4[>Q3(11.11)]were 3.817 and 21.495,respectively;⑤The value of grade 4 applied in predicting the lymphatic metastasis of NSCLC was relatively high with the AUC of 0.804(SE:0.023,P<0.001);⑥The relative expression of MMP-7,MMP-9 and VEGF mRNA were higher in invasive carcinoma than in superificial carcinoma.The relative expression of MMP-7,MMP-9 and VEGF mRNA were higher in NSCLC patients with lymphatic metastasis than in NSCLC patients without lymphatic metastasis.Conclusions:The expression of HOTAIR was associated with the invasiveness and lymphatic metastasis of NSCLC.The expression of HOTAIR had a moderate value when applied in predicting the invasiveness of NSCLC,and had a relatively high value when applied in predicting lymphatic metastasis of NSCLC.The potential mechanism of the enhancement of the invasiveness lymphatic metastasis of NSCLC by HOTAIR was via the up-regulation of MMP-7,MMP-9 and VEGF expression.