Relationship Between Poly-miRTS Of VEGFA And VEGFR1 With Prognosis Of Non Small-Cell Lung Cancer

Objective:Lung cancer, a severely threaten to the health and life, is one of the most common malignant tumors. Disease incidence is rising year by year, of which 80% for non-small cell lung cancer (NSCLC). As the majority of cases have been confirmed to the medium and late stage when it was diagnosed, so doctors can’t predict the curative effect and prognosis by detect protein expression level and RNA level of tumors tissue. The growth of every organ and tissue need the nutrients that was provided by blood vessels, therefore the growth and metastasis of lung cancer is no exception. When the size of tumor is more than 1-2mm3, in order to maintain the ability of infinite proliferation, body will secrete some growth factors which can stimulate angiogenesis and mature blood vessel. The strongest growth factor is vascular endothelial growth factors (VEGF) that can promoting the proliferation of vascular endothelial cells directly and enhance the permeability of blood vessels. In recent years, the relation between the development of NSCLC and the anomaly of gene transcription and post transcriptional regulation had confirmed by numerous studies. Now, more and more researchers put the functions of small RNA (miRNA) as a key direction. MicroRNA is a nucleotide sequence that is a highly conservative form, but also can regulate the expressions of eukaryotic gene. It regulate the expressions of target mRNA in the transcription and post transcription, especially it is involved in cell proliferation、apoptosis and metastasis in the development process of malignant tumors.This study was conducted to determine the impact of potentially functional polymorphisms in the VEGFA and VEGFRl genes on the survival of medium and late stage non-small cell lung cancer (NSCLC) patients.Methods:We used SNP database and selected 11 SNPs with minor allele frequency more 10% in the promoter and gene region. The SNPs were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The association study was analyzed between the polymorphisms located VEGFA and VEGFR1 genes and survival in patients with non-small cell lung cancer. Furthermore, the function study was applied by luciferase assay. Finally, using statistical analysis software to the results and data processing and analysis, to determine whether the experimental results with statistical significance.Results:Patients with the VEGFA-rs3025039C<T genotype had a significantly decreased OS (under a referent model Log rank p 0.005) and DFS (under a referent model Log rank p 0.03). The VEGFA-rs3025039C promoter activity increased compare to rs3025039T (p 0.003).In conclusion, the rs3025039 gene may be used to as a marker that could predict the survival rate of NSCLC patients after chemotherapy.