Predicting 5-fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: Three-gene expression model predicts clinical response
Predicting 5-fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: Three-gene expression model predicts clinical response
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DOI：
10.1002/ijc.21843
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发表时间：
2006-07-15
影响因子：
6.4
通讯作者：
Shimada, Hiroshi
中科院分区：
文献类型：
--
作者：
Matsuyama, Ryusei;Togo, Shinji;Shimada, Hiroshi
我们鉴定了结直肠癌中与 5-氟尿嘧啶 (5-FU) 敏感性相关的基因，并利用这些基因来预测肝转移的 5-FU 敏感性。先前使用 cDNA 微阵列鉴定了涉及胃癌和结肠癌细胞系 5-FU 抗性的 81 个候选基因。在本研究中，使用实时定量 RT-PCR 检测 22 名患者原发性结直肠肿瘤手术切除的材料，测量了这 81 个选定基因和 5-FU 相关酶基因的 mRNA 表达水平，包括胸苷酸合成酶 (TS)、二氢嘧啶脱氢酶 (DPD) 和乳清酸磷酸核糖基转移酶 (OPRT)。通过评估基于 5-FU 的肝动脉注射 (HAI) 化疗对同时性肝转移的效果来评估临床反应。四种基因（TNFRSF1B、SLC35F5、NAG-1 和 OPRT）在 5-FU 无反应和反应肿瘤中具有显着不同的表达谱 (p < 0.05)。然后使用判别分析开发了使用三个基因（TNFRSF1B、SLC35F5 和 OPRT）的“反应指数”系统；结果与个体的化疗敏感性密切相关。在我们的反应指数中得分为阳性的 11 例患者中，有 9 例在基于 5-FU 的化疗后实现了肝转移的减少，而评分为负的 11 例中只有 1 例对化疗反应良好。我们的“反应指数”系统由 TNFRSF1B、SLC35F5 和 OPRT 组成，在预测基于 5-FU 的化疗对结直肠癌肝转移的疗效方面具有巨大潜力。 (c) 2006 Wiley-Liss, Inc.
We identified genes related to 5-fluorouracil (5-FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5-FU sensitivity of liver metastases. Eighty-one candidate genes involved in 5-FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5-FU-related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real-time quantitative RT-PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5-FU-based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG-1 and OPRT) had significantly different expression profiles in 5-FU-nonresponding and responding tumors (p < 0.05). A "Response Index" system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5-FU-based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our "Response Index" system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5-FU-based chemotherapy against liver metastases from colorectal cancer. (c) 2006 Wiley-Liss, Inc.