Differential Research Of Expression Of VEGF-A,VEGFR2 And Notch1 In Different Pathological Tissue Types Of Lung Cancer

BackgroundLung cancer is the most frequently occurring malignancy and the leading cause of death in China.And its incidence is increasing year by year.In addition to surgery,radiotherapy,chemotherapy and targeted therapy of gene mutation,targeted therapy of anti-tumor angiogenesis is also among the research hotspots.Tumor angiogenesis is an extremely complex process,which is regulated by the interaction and coinduction of multiple signaling pathways and pathways.VEGF(vascular endothelial growth factor)-VEGFR(vascular endothelial growth factor receptor)is one of the common signalpathways.Althoughtheanti-VEGFdrug,bevacizumab,has obtained some outcomes in non-small cell lung cancer and bevacizumab combined with chemotherapy has been recommended for the treatment of advanced,metastatic and recurrent non squamous non-small cell lung cancer cell according to the latest NCCN guidelines,but there were still some patients who failed to respond to the treatment.Futhermore,more and more researchers have noticed the drug resistance problem.As a result,more anti-angiogenic signaling pathways are needed.Now,the most studied research is the Delta(Delta like ligand 4)-Notch signaling pathway,and there is a mutual regulation between the two pathways.To discover whether there is significant difference in the expression of vascular signaling pathway in different lung cancer pathological types and whether it can provide a theoretical basis for the further individualized anti-vascular targeting therapy,more further researches are needed.ObjectiveTo study the differential expressionof VEGF-A,VEGFR2 and Notch1 in lung cancer in different pathological types,the relationship among VEGF-A,VEGFR2 and Notch1 and the correlation between VEGF-VEGFR pathway and Delta-Notch pathway and to provide a reference for clinical selection of anti-angiogenic drugs on lung cancer individualized therapy.Meanwhile,we conducted this study to find new therapeutic targets and provide a new direction for the treatment of lung cancer.Methods1.All specimens were extracted from the lung cancer surgery patients from 2009 to2017 at Qingdao Municipal hospital.There were 110 cases,including 75 male cases and35 female cases.The age ranged from 29 to 87 years old.The average age was 59 years old.Among the 110 cases,35 cases were squamous cell carcinoma,35 cases were adenocarcinoma and 40 cases were small cell lung cancer.The diagnosis had been confirmed by both pathological and immunohistochemical detection.20 cases of adjacent tissues of cancer were selected as the control group.The expression level of VEGF-A,VEGFR-2 and Notch1 protein in the tissue was determined by immunohistochemistry.2.Statistical analysis:Analyses were performed using SPSS24.0 software.x~2test and spearman rank correlation analysis were used to compare the indexes among different groups.p<0.05 indicates that the difference is statistically significant.Results1.The expression of VEGF-A and VEGFR2 in lung cancer,whether in non-small cell lung or small cell lung cancer,was significantly higher than that in adjacent tissues of cancer(x~2=13.125,12.303,17.062,14.354,p<0.01).The expression of Notch1 in non-small cell carcinoma was higher than that in adjacent tissues of cancer(x~2=9.498,p<0.01),while the expression in small cell lung cancer was significantly lower than that in adjacent tissues of cancer(x~2=9.624,p<0.01).2.There was a positive correlation among the expression of VEGF-A,VEGFR2and Notch1 in non-small cell lung cancer(rs=0.652,0.374,0.418,p<0.01),However,there was a positive correlation between the expression of VEGF-A and VEGFR2 in small cell lung cancer(rs=0.557,p<0.01),and Notch1 negatively correlated with VEGF-A and VEGFR2 expression(rs=-0.385,-0.458,p<0.05,p<0.01).3.The expression of VEGF-A,VEGFR2 and Notch1 in patients with non-small cell lung cancer had no correlation with their age,sex and pathological type(p>0.05),but it significantly correlated with lymph node metastasis,clinical stage and differentiation degree(p<0.05).4.The difference between the expression of VEGF-A and VEGFR2 in non-small cell lung cancer and small cell lung cancer was not statistically significant(p>0.05),while the expression of Notch1 was significantly different(x~2=50.307,p<0.01).ConclusionThe anti-VEGF signaling pathway drugs may have a certain prospect in the treatment of small cell lung cancer.Notch1 has a carcinogenic effect in non-small cell lung cancer,but it may play a role in inhibiting cancer in small cell lung cancer.The regulation mechanism of Notch signal to VEGF-VEGFR pathway in different tissues of lung cancer is different.In non-small cell lung cancer,there may exist a positive regulatory mechanism.While in small cell lung cancer,it may be a negative regulatory mechanism,which needs further study.