| Objective:The paper aims to investigate the correlation between Polymorphism of TYMS、GSPT1 gene and chemotherapy of PP/ PC to patients with advanced NSCLC. It provides the reference for further study on individualized therapy and chemotherapy sensitivity of Pemetrexed Combined Platinum Chemotherapy to advanced NSCLC.Methods:30 cases of advanced non-small cell lung cancer have been selected to finish the study during the period from 1st January, 2013 to 1st January, 2015. Before the first Pemetrexed Combined Platinum Chemotherapy, 2 millimeters vein blood had been extracted from those 30 cases to analyze genomic DNA. The patients gene were grouped by using Real-time PCR technology to test the polymorphism of TYMS, GSTP1. Follow- up study was applied to investigate the relationship between the Polymorphism of TYMS/GSTP1 and the sensitivity of Pemetrexed Combined Platinum chemotherapy.Results:Conclusions:1.In the study of 30 cases, 3 genotypes of GSTP1 exited in the 105 th animo acid sites of GSTP1 gene. GSTP1 genotype frequencies were A/A(60%), A/G(36.3%) and G/G(3.3%). According to28 bp tandem repeat exited in 5 UTR, TYMS gene was divided into 3 types: 2R/2R(3.3%), 2R/3R(43.4%), 3R/3R(53.3%).。2.Among 14 immunocytochemical cases, the positive frequencies of TYMS protein were 64.3%(9/14), the negative frequencies were 35.7(5/14). 2R/2R&2R/3R were low express group, 3R/3R was high express group. TYMS genotype(2R/3R, 3R/3R) and TYMS protein expression existed negative correlation(γ= 0.757,P=0.036)3. In the single factor analysis, efficiency of patients with G allele in GSTP1(I105V) were significantly higher than those with A/A genotype(58.3% vs. 16.7%, P<0.05). The median PFS was significantly longer than A/A(5.7 months vs. 4.0 months, P=0.047). Age, differentiation, stage, short-term remission were not statistically different with PFS.4. In the single factor analysis, there was no statistical difference between TYMS gene and recent efficiency(P>0.05), but different from patients’ PFS. The median PFS of patients with 3R/3R genotype and of patients with 2R/3R genotype were significantly different(4.3 months vs. 7.8 months, P=0.036).5. With Cox proportional hazard model analyzing, Sex and genotypes are closely related with PFS(P<0.05). Risk of disease progress of female is 2.12 times as large as male(P<0.05). Risk of disease progress of patients with TYMS(3R/3R) genotype is 1.763 times as large as the patient with TYMS(2R/3R) genotype(P<0.05). Risk of disease progress of patients with genotype of AA in GSTP1(I105V) site is 1.537 times as large as patient with G allele(P<0.05).Conclusion:1. In PP/PC therapy of patients with advanced NSCLC, the efficacy of patients with TYMS(2R/3R) and G allele in GSTP1(I105V) and PFS were higher than those with A/A. PFS of patients with 5 UTR in TYMS(2R/3R) was longer than those with 3R/3R.2. The testing results of polymorphism of TYMS 2R/3R and GSTP1(I105V) could be the one of the reference index to predict Pemetrexed Combined Platinum Chemotherapy to patients with advanced NSCLC.。3.TYMS gene(2R/3R) of peripheral blood leukocytes of patients with advanced non-small cell lung cancer might reflect the content of thymidylate synthase in tumor cells of patients with advanced NSCLC. |
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