非小细胞肺癌中根据组织学类型划分的与培美曲塞敏感性相关的分子因素

Molecular Factors Associated with Pemetrexed Sensitivity According to Histological Type in Non-small Cell Lung Cancer.

作者信息

Yoshida Tsukihisa, Okamoto Tatsuro, Yano Tokujiro, Takada Kazuki, Kohno Mikihiro, Suda Kenichi, Takenoyama Mitsuhiro, Oda Yoshinao, Maehara Yoshihiko

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Clinical Research Institute, National Hospital Organization Beppu Medical Center, Beppu, Japan.

出版信息

Anticancer Res. 2016 Dec;36(12):6319-6326. doi: 10.21873/anticanres.11228.

DOI:10.21873/anticanres.11228

PMID:27919952

Abstract

BACKGROUND

This study was designed to investigate potential molecules that predict chemosensitivity to pemetrexed (Alimta®) in surgically resected non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS

Chemosensitivity to ALM and other drugs was assessed by succinate dehydrogenase inhibition (SDI) test in 69 NSCLC samples (55 adenocarcinomas, and 14 squamous cell carcinomas). The mRNA expression levels of Alimta®-target enzymes [thymidylate synthase (TYMS); dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT)], Alimta®-metabolizing enzymes [γ-glutamyl hydrase (GGH) and folylpolyglutamate synthase] and an Alimta® transporter [reduce folate carrier (RFC)] were measured and examined for potential correlations to chemosensitivity.

RESULTS

The squamous cell carcinoma samples showed higher TYMS expression and lower RFC expression than did the adenocarcinoma samples. In the adenocarcinoma sample analyses, GGH expression was inversely correlated to sensitivity.

CONCLUSION

The histology-dependent differences in chemosensitivity to Alimta® may be attributed to the histology-dependent differences in TYMS and RFC expression. In adenocarcinomas, GGH potentially represents a marker for chemosensitivity to Alimta®.

摘要

背景

本研究旨在探究可预测手术切除的非小细胞肺癌（NSCLC）对培美曲塞（力比泰®）化疗敏感性的潜在分子。

材料与方法

通过琥珀酸脱氢酶抑制（SDI）试验评估69例NSCLC样本（55例腺癌和14例鳞状细胞癌）对力比泰及其他药物的化疗敏感性。测定力比泰靶向酶[胸苷酸合成酶（TYMS）；二氢叶酸还原酶（DHFR）和甘氨酰胺核糖核苷酸甲酰基转移酶（GARFT）]、力比泰代谢酶[γ-谷氨酰水解酶（GGH）和叶酰聚谷氨酸合成酶]以及力比泰转运体[还原型叶酸载体（RFC）]的mRNA表达水平，并检测其与化疗敏感性的潜在相关性。