MDR1 T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese
MDR1 T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese
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DOI：
10.1248/bpb.29.1449
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发表时间：
2006-07-01
影响因子：
2
通讯作者：
Okumura, Katsuhiko
中科院分区：
文献类型：
--
作者：
Koyama, Tatsuya;Nakamura, Tsutomu;Okumura, Katsuhiko
我们在21例日本患者的结直肠腺癌和邻近非癌结直肠组织中评估了MDR1 mRNA的表达水平。前者低于后者（p=0.012），提示其下调可能是结直肠组织恶性转化的结果，可能与分化抑制有关。中分化结直肠腺癌中表达较低，但差异无统计学意义（p=0.111）。在一株结直肠癌细胞系HCT-15中，经丁酸钠和全反式维甲酸两种典型分化剂治疗后，发现MDR1 mRNA表达上调，提示其参与细胞事件，导致分化而未发生恶性转化。MDR1 T- 129c与MDR1 mRNA在结直肠腺癌（p=0.040）和邻近非癌性结直肠组织（p=0.023）中的低表达相关，而G2677A、T和C3435T与MDR1 mRNA的低表达相关，可能是预测结直肠腺癌低分化的有用侵入性标志物，从而预测患者预后不良，特别是在没有额外活检样本的情况下。应该对相对较多的患者进行进一步调查，以证实这些初步结果。
The expression level of MDR1 mRNA was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues obtained from 21 Japanese patients. It was lower in the former than in the latter (p=0.012), suggesting its down-regulation as a consequence of malignant transformation of colorectal tissues, possibly with the suppression of differentiation. Relatively lower expression was suggested in moderately-differentiated colorectal adenocarcinomas than well-differentiated ones, but there was no statistical difference (p=0.111). MDR1 mRNA up-regulation was found in a colorectal adenocarcinoma cell line, HCT-15, after treatment with two typical differentiating agents, sodium butyrate and all-trans retinoic acid, suggesting its involvement in the cellular events, resulting in differentiation without malignant transformation. MDR1 T-129C, but not G2677A,T and C3435T, was associated with the lower expression of MDR1 mRNA both in colorectal adenocarcinomas (p=0.040) and adjacent noncancerous colorectal tissues (p=0.023), possibly being an useful invasive marker predicting poorly-differentiated colorectal adenocarcinomas and thereby the poor prognosis of the patients, especially when no extra biopsy samples will be obtained. Further investigations with relatively large number of patients should be undertaken to confirm these preliminary results.