The Study On Gene Polymorphisms Of Folate Metabolic Enzyme And Efficacy Of Pemetrexed In Patients With Advanced Lung Adenocarcinoma

Background and PurposePemetrexed combined with platinum is the most common first-line chemotherapy for non-small cell lung cancer(NSCLC)for epidermal growth factor receptor(EGFR)wild-type patients and an alternative to the failure of EGFR inhibitors.Previous studies have shown that single nucleotide polymorphisms of drug-metabolizing enzymes and drug transporter-related genes have a good predictive value for the efficacy,adverse reactions and survival of chemotherapeutic drugs.In this study,we detect single nucleotide polymorphisms of reduced folate carrier(SCL19A1),folic acid polyglutamate synthase(FPGS),dihydrofolate reductase(DHFR)and glutamylhydrolase(GGH)and explore its correlation with pemetrexed combined with cisplatin in advanced lung adenocarcinoma.MethodPatients with stage IIIb or stage IV adenocarcinoma who were referred to the Department of Oncology,the Second Affiliated Hospital of Dalian Medical University from January 2016 to January 2017 were enrolled.All patients were confirmed by pathology and immunohistochemistry and received pemetrexed combined with cisplatin regimen chemotherapy.We take the patient's peripheral blood 5ml by EDTA vacuum anticoagulation blood vessels before chemotherapy.The single nucleotide polymorphisms of SLC19A1,FPGS,DHFR and GGH in peripheral blood of patients were detected by Snap Shot method and explore its correlation with pemetrexed combined withcisplatin in advanced lung adenocarcinoma.SPSS22.0 software was used for statistical analysis,It is considered that P<0.05 has statistically significant difference.Unconditional Logistic regression analysis was used to analyze the association of single nucleotide polymorphisms(SNPs)with the efficiency of chemotherapy.The relationship between each SNP site and patients' progression-free survival time(PFS)is analyzed by Kaplan-Meier analysis.Result1.A total of 60 patients were enrolled,and all received the first-line chemotherapy of pemetrexed combined with cisplatin(AP).The results of unconditional Logistic regression analysis showed that there was no significant correlation between the patients' gender,age,smoking status,staging and EGFR mutation status(P>0.05).2.The effective rates of GG,GA and AA genotypes were 54.5%,16.2% and 41.7%respectively in 60 patients with SLC19A1rs1051266.The response rate of patients with GG genotype was significantly higher than that of patients with GA genotype(P=0.017;OR=0.151).The median PFS for the three genotypes was 6 months,7 months and 8months,respectively,with no significant difference(P>0.05).The effective rates of CC,CT and TT genotype chemotherapy in 60 patients with rs1051298 were 36.4%,24.3%and 10.8%,respectively.There was no significant correlation between genotype and chemotherapy efficiency(P>0.05).The median PFS for the three genotypes was 6months,7 months and 6.5 months,respectively,with no significant difference(P>0.05).3.The effective rates of GG,GA and AA genotypes in 60 patients with FPGS rs10106 were 28.6%,28.6% and 25.0%,respectively.There was no significant correlation between the three genotypes and chemotherapy efficiency(P>0.05).The median PFS for the three genotypes was 7 months,7 months and 11.5 months,respectively,with no significant difference(P>0.05).The effective rates of CC,CT and TT genotype chemotherapy in 60 patients with rs1544105 were 71.4%,19.4% and 27.3%,respectively.Chemotherapy in patients with genotype CC was significantly more effective than in patients with CT.(P=0.033;OR=0.111).The median PFS for the three genotypes was 6 months,7 months and 7 months,respectively,with no significantdifference(P>0.05).4.The effective rates of CC,CT and TT genotype in 60 patients with DHFRrs1650-697 were 33.3%,27.6% and 14.3%,respectively.There was no significant correlation between the three genotypes and chemotherapy efficiency(P>0.05).The median PFS for the three genotypes were 7 months,7 months and 6 months,respectively,with no significant difference(P>0.05).5.The effective rates of CC,CT and TT genotype chemotherapy in 60 patients with GGHrs11545078 were 26.4% and 42.3%,respectively.There was no significant correlation between the three genotypes and chemotherapy efficiency(P>0.05).The median PFS for all three genotypes was 7months and 5 months,with no significant difference(P> 0.05).conclusion1.SLC19A1rs1051266 GG genotype and FPGSrs1544105 CC genotype patients with chemotherapy is more efficient,and It is suggested that SLC19A1rs1051266 and FPGSrs1544105 single nucleotide polymorphisms may be effective predictors of pemetrexed efficacy.2.There was no significant correlation between single nucleotide polymorphism of ST19191051298,FPGSrs10106,DHFRrs1650697 and GGHrs11545078 and the efficacy of pemetrexed.3.Single nucleotide polymorphism of SLC19A1,FPGS,DHFR and GGH gene had no significant correlation with PFS.