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

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.

• Authors: Satoshi Fukuda, Tetsuya Oguri, Eiji Kunii, Kazuki Sone, Takehiro Uemura, Osamu Takakuwa, Ken Maeno, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Akio Niimi
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 102 Pg. 15-20 (12 2016) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 27987582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Organoplatinum Compounds
• Pemetrexed
• Peptide Synthases
• folylpolyglutamate synthetase

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, enzymology, genetics, pathology)
• Cell Line, Tumor
• Disease-Free Survival
• Female
• Humans
• Lung Neoplasms (drug therapy, enzymology, genetics, pathology)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Pemetrexed (administration & dosage)
• Peptide Synthases (genetics, metabolism)
• Polymorphism, Single Nucleotide
• Predictive Value of Tests
• Treatment Outcome