title: A folylpoly-γ-glutamate synthase single nucleotide polymorphism associated with response to pemetrexed treatment combined with platinum for non-small cell lung cancer.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  FPGS SNP 2572C>T is a predictive marker of the efficacy of PEM and platinum drugs for NSCLC.
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: es-fukuda@hotmail.co.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: t-oguri@med.nagoya-cu.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.affiliation: Department of Respiratory Medicine, Nagoya City West Medical Center, 1-1-1 Hirate-cho, Kita-ku, Nagoya 462-8508, Japan. Electronic address: eiji_921@icloud.com.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kunii
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: k-sone@med.nagoya-cu.ac.jp.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sone
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: tuemu@med.nagoya-cu.ac.jp.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: takakuwa@med.nagoya-cu.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takakuwa
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: kmaeno@med.nagoya-cu.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Maeno
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: kaney32@med.nagoya-cu.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: hohkubo@med.nagoya-cu.ac.jp.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohkubo
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: mtake19@med.nagoya-cu.ac.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takemura
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: yutaka@med.nagoya-cu.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: a.niimi@med.nagoya-cu.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000068437:Pemetrexed / Q000008:administration & dosage; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000068437:Pemetrexed; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase
keywords: 2572C>T; Folylpoly-γ-glutamate synthase; Pemetrexed; Single nucleotide polymorphism