A folylpoly-γ-glutamate synthase single nucleotide polymorphism associated with response to pemetrexed treatment combined with platinum for non-small cell lung cancer. (December 2016)

• Record Type: Journal Article
• Authors: Fukuda, Satoshi; Oguri, Tetsuya; Kunii, Eiji; Sone, Kazuki; Uemura, Takehiro; Takakuwa, Osamu; Maeno, Ken; Kanemitsu, Yoshihiro; Ohkubo, Hirotsugu; Takemura, Masaya; Ito, Yutaka; Niimi, Akio
• Is Part Of: Lung cancer. Volume 102(2016)
• Page Start: 15
• Page End: 20
• Publication Date: 2016-12
• Subjects: SNP single nucleotide polymorphism -- FPGS folylpoly-γ-glutamate synthase -- PEM pemetrexed -- MTX methotrexate -- NSCLC non-small cell lung cancer -- Bev bevacizumab -- TS thymidylate synthase -- DHFR dihydrofolate reductase -- GARFT glycinamide ribonucleotide formyltransferase -- AICARFT aminoimidazole carboxamide ribonucleotide formyltransferase -- CDDP cisplatin -- CBDCA carboplatin -- PFS progression free survival -- OS overall survival -- RR response rate -- Bev(−) no addition of bevacizumab -- Bev(+) addition of bevacizumab -- CBP cAMP response element binding protein; Folylpoly-γ-glutamate synthase -- Single nucleotide polymorphism -- 2572C > T -- Pemetrexed; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.10.006
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: There was a correlation between FPGS protein expression and the sensitivity to PEM in lung cancer cell line. There was a correlation between FPGS protein expression and a FPGS SNP. The FPGS SNP is a determinats for response to PEM with platinum drugs in NSCLC. Abstract: Objectives: In this study, we investigated whether single nucleotide polymorphisms (SNPs) in folylpoly-γ-glutamate synthase (FPGS), which catalyzes the polyglutamation of pemetrexed (PEM), is related to FPGS expression and the response to PEM in non-small cell lung cancer (NSCLC). Materials and methods: We first examined FPGS protein expressions according to FPGS SNPs genotype groups in 15 lung adenocarcinoma cell lines. Next, 101 non-squamous NSCLC patients treated with PEM and platinum drugs were classified into FPGS SNP genotype groups to investigate the relation between FPGS SNP genotypes and treatment outcome. Results: When the 15 adenocarcinoma cell lines were classified into FPGS SNP 2572C > T genotype groups, we found that the FPGS protein expression was significantly higher in the CC genotype group than in the TT + CT genotype group (p = 0.0022). In contrast, there was no significant difference in FPGS expression when another FPGS SNP was analyzed. We also examined the FPGS SNP 2572C > T genotype in 101 non-squamous NSCLC patients treated with PEM and platinum drugs. Among these 101 patients, response rate was significantly higher in the CC genotype group than in the TT + CT genotype group (p = 0.0034). When we examined the patients treated with PEM, platinum drugs and Bev, almost all (29/33) were classified into the TT + CT genotype group. The response rate, progression-free survival, and over-all survival were all significantly better in the patients of the TT + CT genotype group who also received Bev than in those who did not receive Bev (p = 0.034, 0.021, 0.018, respectively). Conclusion: FPGS SNP 2572C > T is a predictive marker of the efficacy of PEM and platinum drugs for NSCLC.