Fakhrejahani Elham, Miyamoto Akiko, Tanigawa Nobuhiko
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki-shi, Osaka 569-8686, Japan.
Cancer Chemother Pharmacol. 2007 Aug;60(3):437-46. doi: 10.1007/s00280-007-0448-1. Epub 2007 Mar 22.
It has been suggested that the gene expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) help in the prediction of the response to 5-fluorouracil (5-FU) in vivo and in vitro in gastric cancers.
In this study, intratumoral TS and DPD gene expressions were evaluated with real time reverse transcriptional polymerase chain reaction technique to determine the correlation between the expression of these two genes and in vitro sensitivity to 5-FU, assessed by the histoculture drug response assay on 87 patients with gastric adenocarcinoma.
The sensitivity to 5-FU did not show any difference in clinicopathological groups. DPD gene level was higher in undifferentiated (n = 39) than differentiated (n = 48) tumors (P = 0.043). In differentiated tumors, TS gene expression levels were higher in the tumors with relative resistance to 5-FU, while in undifferentiated cases, DPD mRNA levels were higher in tumors that showed resistance to 5-FU in vitro (P = 0.043 and 0.007, respectively). DPD also had significant predictive value for 5-FU sensitivity in undifferentiated cases [R(S) = -0.401, P = 0.011]. TS and DPD gene expression levels were more highly correlated in undifferentiated compared to differentiated cases [R(S) = 0.515 and 0.359, respectively].
Different gene expression might be responsible for 5-FU sensitivity in gastric cancers of different histologic origin.
有人提出，胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）的基因表达水平有助于预测胃癌体内和体外对5-氟尿嘧啶（5-FU）的反应。
在本研究中，采用实时逆转录聚合酶链反应技术评估肿瘤内TS和DPD基因表达，以确定这两个基因的表达与87例胃腺癌患者体外对5-FU敏感性之间的相关性，体外敏感性通过组织培养药物反应试验进行评估。
5-FU敏感性在临床病理组中未显示出任何差异。未分化肿瘤（n = 39）中的DPD基因水平高于分化肿瘤（n = 48）（P = 0.043）。在分化肿瘤中，对5-FU相对耐药的肿瘤中TS基因表达水平较高，而在未分化病例中，体外对5-FU耐药的肿瘤中DPD mRNA水平较高（分别为P = 0.043和0.007）。DPD对未分化病例中的5-FU敏感性也具有显著的预测价值[R(S) = -0.401，P = 0.011]。与分化病例相比，未分化病例中TS和DPD基因表达水平的相关性更高[分别为R(S) = 0.515和0.359]。
不同组织学来源的胃癌中，5-FU敏感性可能由不同的基因表达所致。
