Akamoto Shintaro, Usuki Hisashi, Haba Reiji, Kakinoki Keitarou, Okano Keiichi, Izuishi Kunihiko, Wakabayashi Hisao, Suzuki Yasuyuki
Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hepatogastroenterology. 2008 Sep-Oct;55(86-87):1882-6.
BACKGROUND/AIMS: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are reported to be a major determinant of variations in the sensitivity for fluoropyrimidines in gastric cancer. The aim of this study was to investigate whether there is a discrepancy in the TS and DPD expression depending on measuring method.
The protein levels and mRNA level of TS and DPD were estimated in primary gastric cancer tissue specimens after a non-curative resection. The protein levels were determined by ELISA from frozen tissue specimens. The gene expressions were measured using real-time reverse transcriptional polymerase chain reaction (RT-PCR). For the extraction of RNA, laser-captured microdissection (LCM) was performed in formalin-fixed paraffin-embedded (FFPE) specimens.
There was no correlation between the protein levels and mRNA levels of TS and DPD. The protein levels and mRNA expression levels were not correlated with survival. High levels of TS mRNA showed a trend toward reduced survival (p=0.074).
The discrepancy in TS and DPD expressions depending on the measurement methodologies utilized should thus be emphasized in these far advanced gastric cancer patients.
背景/目的：据报道，胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）是胃癌对氟嘧啶敏感性差异的主要决定因素。本研究的目的是调查根据测量方法，TS和DPD表达是否存在差异。
在非根治性切除后的原发性胃癌组织标本中评估TS和DPD的蛋白质水平和mRNA水平。通过酶联免疫吸附测定法（ELISA）从冷冻组织标本中测定蛋白质水平。使用实时逆转录聚合酶链反应（RT-PCR）测量基因表达。为了提取RNA，在福尔马林固定石蜡包埋（FFPE）标本中进行激光捕获显微切割（LCM）。
TS和DPD的蛋白质水平与mRNA水平之间无相关性。蛋白质水平和mRNA表达水平与生存率无关。TS mRNA高水平显示出生存率降低的趋势（p = 0.074）。
因此，在这些晚期胃癌患者中，应强调根据所采用的测量方法，TS和DPD表达存在差异。
