Sakon Kayo, Sasaki Masato, Tanaka Kaede, Mizunaga Tae, Yano Keita, Kawamura Yuuko, Okada Akitoshi, Ikeda Takeshi, Tanabe Sawaka, Takamori Atsushi, Yamada Narihisa, Morioka Kouichi, Koshiji Takaaki
Department of Surgery (II), Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka Eiheijichou, Fukui, 910-1193, Japan.
Department of Thoracic Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjyuku-ku, Tokyo, 162-8655, Japan.
Discov Oncol. 2021 Jun 25;12(1):19. doi: 10.1007/s12672-021-00413-w.
Various factors related to the sensitivity of non-small cell lung carcinoma (NSCLC) to 5-fluorouracil (5-FU) have been reported, and some of them have been clinically applied. In this single-institutional prospective analysis, the mRNA expression level of five folic acid-associated enzymes was evaluated in surgical specimens of NSCLC. We investigated the correlation between the antitumor effect of 5-FU in NSCLC using an anticancer drug sensitivity test and the gene expression levels of five enzymes.
Forty patients who underwent surgery for NSCLC were enrolled, and the antitumor effect was measured using an in vitro anticancer drug sensitivity test (histoculture drug response assay) using freshly resected specimens. In the same sample, the mRNA expression levels of five enzymes involved in the sensitivity to 5-FU were measured in the tumor using real-time PCR. The expression levels and the result of the sensitivity test were compared.
No correlation was found between dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), or DPD/OPRT expression and the antitumor effects of 5-FU. On the other hand, a correlation was found between thymidylate synthase (TS), folylpoly-c-glutamate synthetase (FPGS), and dihydrofolate reductase (DHFR) expression and 5-FU sensitivity.
Expression of FPGS and DHFR may be useful for predicting the efficacy of 5-FU-based chemotherapy for NSCLC.
已有报道多种与非小细胞肺癌（NSCLC）对5-氟尿嘧啶（5-FU）敏感性相关的因素，其中一些已应用于临床。在这项单机构前瞻性分析中，评估了NSCLC手术标本中五种叶酸相关酶的mRNA表达水平。我们使用抗癌药物敏感性试验研究了NSCLC中5-FU的抗肿瘤作用与这五种酶的基因表达水平之间的相关性。
纳入40例行NSCLC手术的患者，使用新鲜切除的标本通过体外抗癌药物敏感性试验（组织培养药物反应测定）测量抗肿瘤作用。在同一样本中，使用实时PCR测量肿瘤中与5-FU敏感性相关的五种酶的mRNA表达水平。比较表达水平和敏感性试验结果。
未发现二氢嘧啶脱氢酶（DPD）、乳清酸磷酸核糖转移酶（OPRT）或DPD/OPRT表达与5-FU的抗肿瘤作用之间存在相关性。另一方面，发现胸苷酸合成酶（TS）、叶酰聚谷氨酸合成酶（FPGS）和二氢叶酸还原酶（DHFR）表达与5-FU敏感性之间存在相关性。
FPGS和DHFR的表达可能有助于预测基于5-FU的化疗对NSCLC的疗效。
