A Platinum Agent Resistance Gene, POLB, Is a Prognostic Indicator in Colorectal Cancer
A Platinum Agent Resistance Gene, POLB, Is a Prognostic Indicator in Colorectal Cancer
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DOI：
10.1002/jso.21275
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发表时间：
2009-09-01
影响因子：
2.5
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Iwatsuki, Masaaki;Mimori, Koshi;Mori, Masaki
背景资料：铂类药物化疗的最新进展改善了结直肠癌（CRC）的临床结局，但没有有用的标志物来预测此类药物的疗效。DNA聚合酶β（POLB）通过DNA修复机制介导化疗的疗效。我们分析了POLB表达在CRC化疗及其作为预后指标的潜力的意义：使用微阵列，POLB被发现在CRC细胞中过表达与相应的正常结肠上皮细胞相比。我们测定了POLB抑制细胞对顺铂和奥沙利铂的敏感性。我们评估了97例结直肠癌中POLB mRNA的表达，以确定POLB表达的临床病理学意义。结果：我们发现抑制POLB改变了对顺铂的体外敏感性，但对奥沙利铂没有影响。97例大肠癌中，高POLB组的淋巴结转移、远处转移及TNM分期均显著高于低POLB组（P < 0.05）。POLB高表达者预后明显差于低表达者（P < 0.05）。结论：POLB在高恶性潜能的大肠癌中过度表达。我们建议POLB可能是一个有用的预测指标，选择病人，对顺铂有反应。外科肿瘤学杂志2009;100：261-266. (C)2009 Wiley-Liss，Inc.
Background: Recent progress in chemotherapy with platinum agents has improved clinical outcome in colorectal cancer (CRC), but there are no useful markers to predict the efficacy of such agents. DNA polymerase beta (POLB) mediates the efficacy of chemotherapy through DNA repair machinery. We analyzed the significance of POLB expression in CRC chemotherapy and its potential as a prognostic indicator.Methods: Using microarray, POLB was found to be overexpressed in CRC cells compared with corresponding normal colon epithelial cells. We determined the susceptibility of POLB-suppressed cells to cisplatin and oxaliplatin. We evaluated POLB mRNA expression in 97 CRC cases to determine the clinicopathologic significance of POLB expression.Results: We found the suppression of POLB altered the in vitro Susceptibility to cisplatin but not to oxaliplatin. In 97 CRC cases, lymph node metastasis, distant metastasis and TNM classification were significantly greater in the high POLB group than in the low group (P < 0.05). Patients with high POLB expression had significantly poorer prognosis than those with low expression (P < 0.05).Conclusions: The data indicate POLB is overexpressed in CRC cases with high malignant potential. We suggest POLB could be useful as a predictive marker for selection of patient, responsive to cisplatin. J. Surg. Oncol. 2009;100:261-266. (C) 2009 Wiley-Liss, Inc.