Ishihama Hiromi, Chida Masayuki, Araki Osamu, Karube Yoko, Seki Norio, Tamura Motohiko, Umezu Hideo, Honma Koichi, Masawa Nobuhide, Miyoshi Shinichiro
Department of Cardiothoracic Surgery, Dokkyo Medical University, Shimotsuga, Tochigi, Japan.
Jpn J Clin Oncol. 2009 Jan;39(1):33-6. doi: 10.1093/jjco/hyn121. Epub 2008 Nov 17.
A recent meta-analysis study showed that post-operative adjuvant chemotherapy with UFT, an oral combination drug composed of tegafur [prodrug of 5-fluorouracil (5-FU)] and uracil [inhibitor of dihydropyrimidine dehydrogenase (DPD)] was associated with improved survival in patients with lung adenocarcinomas, but not in those with lung squamous cell carcinomas.
We investigated the 5-FU-related gene expression levels of thymidylate synthase (TS), DPD, thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) in resected tumor specimens from 51 patients with adenocarcinomas and 47 with squamous cell carcinomas using quantitative reverse transcription-PCR, and compared those levels between the two histological types.
The relative gene expression values of TS, TP and OPRT were significantly lower in adenocarcinomas compared with squamous cell carcinomas, 1.60 +/- 0.86 versus 4.33 +/- 3.40 (P < 0.001), 0.84 +/- 0.52 versus 2.27 +/- 1.16 (P = 0.006) and 9.59 +/- 6.30 versus 16.94 +/- 12.04 (P < 0.001), respectively. The relative gene expression value of DPD was significantly greater in adenocarcinomas than those in squamous cell carcinomas, 2.33 +/- 1.22 versus 1.50 +/- 1.20 (P = 0.01). Lower expressions of TS and TP were observed more in adenocarcinomas (89.8%) than in squamous cell carcinomas (48.9%) (P < 0.001).
These data may explain that post-operative adjuvant chemotherapy with UFT was associated with improved survival in stage I patients with adenocarcinoma, but less with squamous cell carcinoma.
最近一项荟萃分析研究表明，使用优福定（UFT，一种由替加氟[5-氟尿嘧啶（5-FU）的前体药物]和尿嘧啶[二氢嘧啶脱氢酶（DPD）抑制剂]组成的口服复方药物）进行术后辅助化疗与肺腺癌患者生存率提高相关，但与肺鳞癌患者生存率提高无关。
我们使用定量逆转录聚合酶链反应，调查了51例腺癌患者和47例鳞癌患者切除的肿瘤标本中胸苷酸合成酶（TS）、DPD、胸苷磷酸化酶（TP）和乳清酸磷酸核糖转移酶（OPRT）的5-FU相关基因表达水平，并比较了这两种组织学类型之间的水平。
与鳞癌相比，腺癌中TS、TP和OPRT的相对基因表达值显著更低，分别为1.60±0.86 对4.33±3.40（P<0.001）、0.84±0.52对2.27±1.16（P=0.006）和9.59±6.30对16.94±12.04（P<0.001）。腺癌中DPD的相对基因表达值显著高于鳞癌，为2.33±1.22对1.50±1.20（P=0.01）。腺癌中TS和TP低表达的情况比鳞癌中更多（89.8%对48.9%）（P<0.001）。
这些数据可能解释了使用优福定进行术后辅助化疗与I期腺癌患者生存率提高相关，但与鳞癌患者生存率提高相关性较小。
