The Relationship Between Angiogenic Genes PDGFRA,FGFR3 And FGFR4 And Clinicopathologic Features And Prognosis In Patients With Advanced Non-small Cell Lung Cancer

Objective: Angiogenesis plays an important role in the process of tumor development and metastasis.The purpose of this study was to investigate the relationship between the mutation status of angiogenic genes PDGFRA,FGFR3 and FGFR4 and the clinicopathological characteristics of patients with advanced NSCLC and its effect on the prognosis of patients.Methods: This study collected 163 patients with advanced NSCLC.Patients' medical records,follow-up forms and genetic test reports were inquired,and clinical information of patients was obtained through telephone follow-up,including gender,age,smoking history,pathological type,ECOG score,tumor T stage,presence of lymph node metastasis,EGFR and ALK gene status,first-line treatment,overall survival,and survival outcome.The last follow-up time was March 18,2019,and the survival time was measured in months.The second generation of tumor gene sequencing is to collect the patient's tissue or blood samples,construct the whole genome sequencing library,and then target and enrich the cancer panorama gene,and then target and enrich the library for high-throughput sequencing,and finally obtain the patient's gene mutation results through bioinformatics analysis.SPSS24.0.0.0 software was used for data processing,and mutation rates of PDGFRA,FGFR3 and FGFR4 genes in patients with advanced NSCLC were calculated.The relationship between clinicopathological parameters and mutations of PDGFRA,FGFR3 and FGFR4 genes in patients with advanced NSCLC was analyzed by chi-square test.Logistic regression was used to analyze the first-line efficacy of mutations of PDGFRA,FGFR3 and FGFR4 genes in patients with wild-type and sensitive EGFR mutations.Kaplan-Meier survival curve was used to analyze the relationship between the mutation status of PDGFRA,FGFR3 and FGFR4 genes and the OS of patients with wildtype and sensitive mutations of EGFR.P<0.05 was statistically significant.Results: A total of 163 patients with advanced NSCLC were included in this study.There were a total of 20 patients(12.3%)with PDGFRA gene mutation,mostly in patients with t1-3(P=0.033),lymph node metastasis(P=0.006)and non-adenocarcinoma(P=0.003).There were 21 patients(12.9%)with FGFR3 gene mutation,mostly in patients with ECOG score of 2-3(P=0.025),no lymph node metastasis(P=0.002),and non-adenocarcinoma(P=0.001).There were a total of 48 patients(29.4%)with FGFR4 gene mutation.FGFR4 gene mutation was not correlated with gender,age,smoking history,pathological type,ECOG score,T stage,lymph node metastasis,EGFR and ALK gene mutation status(P>0.05).Due to the different EGFR gene status in advanced NSCLC patients,the treatment methods are different.In the survival analysis,we divided the population into EGFR wild-type and EGFR-sensitive mutants.In the two groups with different EGFR,the gene status of PDGFRA,FGFR3 and FGFR4 had no correlation with the first-line efficacy(P>0.05).The results of survival analysis showed that in patients with EGFR wild-type,PDGFRA gene mutation had no correlation with the survival of patients with advanced NSCLC(P=0.102),while in patients with EGFR-sensitive mutations,the survival time of patients with advanced NSCLC with PDGFRA gene mutation was shorter(P=0.049).Regardless of the EGFR gene status,patients with FGFR3 and FGFR4 gene mutations had significantly shorter OS than patients with wild type(FGFR3: P=0.006,P=0.003).FGFR4: P=0.004,P<0.001).COX regression analysis showed that the two groups with different EGFR got the same results.Univariate analysis showed that high ECOG score(P=0.025,P=0.021),lymph node metastasis(P=0.002,P=0.024),FGFR3 gene mutation(P=0.009,P=0.007)and FGFR4 gene mutation(P=0.009,P<0.01)were associated with a higher risk of death in patients with advanced NSCLC.Multivariate analysis showed that lymph node metastasis(P=0.026;Mutations in FGFR3(P=0.047,P=0.001)and FGFR4(P=0.008,P<0.01)were independent risk factors for survival in NSCLC patients.Conclusion: Mutations in angiogenesis genes FGFR3 and FGFR4 predicted poor prognosis in patients with advanced NSCLC.However,PDGFRA gene mutation was only found in patients with EGFR-sensitive mutations,indicating poor prognosis.