Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
World J Gastroenterol. 2010 Sep 28;16(36):4575-82. doi: 10.3748/wjg.v16.i36.4575.
To prove that the protein expression level of thymidylate synthase is a predictive factor for the response to S-1/cisplatin (CDDP) chemotherapy in gastric cancer.
We measured the protein expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in advanced gastric cancer. Before S-1/CDDP chemotherapy, tumor specimens from primary sites were obtained by endoscopic biopsy and analyzed by enzyme-linked immunosorbent assay. The chemotherapeutic effects on the primary sites were evaluated by endoscopic biopsy performed more than once after S-1/CDDP chemotherapy. The effects are a predictive factor for the response to S-1/CDDP chemotherapy in patients with advanced gastric cancer, as evaluated by endoscopic biopsy over time.
The protein expression level of TS was significantly higher (P < 0.05) in the tumor than in the normal tissue, and significantly lower (P < 0.05) in the responders than in the non-responders. We were able to evaluate the correlation between changes in the protein expression levels of TS, DPD and OPRT and chemotherapeutic responses in 7 patients by assessing tumor tissues more than twice. In the responders, the protein expression level of TS was < 40 ng/mg protein. However, there were significant increases in the protein expression levels of TS (P < 0.01) and DPD (P < 0.05) after chemotherapy in 3 patients. In these cases, the patient assessment changed from "responder" to "non-responder". In the non-responders, the protein expression level of TS was > 40 ng/mg protein.
We have confirmed that the protein expression level of TS is a predictive factor for the response to S-1/CDDP chemotherapy in patients with advanced gastric cancer.
证明胸苷酸合成酶的蛋白表达水平是胃癌对 S-1/顺铂（CDDP）化疗反应的预测因素。
我们测量了晚期胃癌中胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）和乳清酸磷酸核糖基转移酶（OPRT）的蛋白表达水平。在 S-1/CDDP 化疗前，通过内镜活检获得原发部位的肿瘤标本，并通过酶联免疫吸附试验进行分析。在 S-1/CDDP 化疗后多次进行内镜活检评估原发部位的化疗效果。通过随时间进行的内镜活检评估，将其作为晚期胃癌患者对 S-1/CDDP 化疗反应的预测因素。
TS 的蛋白表达水平在肿瘤中明显高于正常组织（P < 0.05），在反应者中明显低于非反应者（P < 0.05）。我们能够通过评估 7 例患者的肿瘤组织超过两次，评估 TS、DPD 和 OPRT 蛋白表达水平变化与化疗反应之间的相关性。在反应者中，TS 的蛋白表达水平<40ng/mg 蛋白。然而，在 3 例患者中，TS（P <0.01）和 DPD（P <0.05）的蛋白表达水平在化疗后明显增加。在这些情况下，患者评估从“反应者”变为“非反应者”。在非反应者中，TS 的蛋白表达水平>40ng/mg 蛋白。
我们已经证实，TS 的蛋白表达水平是晚期胃癌患者对 S-1/CDDP 化疗反应的预测因素。
