Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles
Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles
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DOI：
10.1158/0008-5472.can-05-3834
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发表时间：
2006-04-01
期刊：
影响因子：
11.2
通讯作者：
Nagawa, H
中科院分区：
文献类型：
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作者：
Watanabe, T;Komuro, Y;Nagawa, H
术前放射治疗已被广泛应用于直肠癌的治疗，以改善疾病的局部控制和提高生存率。然而，对放射治疗的反应在个体肿瘤之间是不同的。我们的目标是确定一组可用于表征和预测直肠癌放疗反应的鉴别基因。52例直肠癌患者接受术前放疗进行了研究。在术前放疗前从直肠癌中获得活检标本。通过手术切除标本的组织病理学检查确定对放射治疗的反应，并将其分类为反应者或无反应者。通过使用人U95 Av 2基因芯片测定基因表达谱，我们鉴定了33个新的识别基因，其表达在应答者和非应答者之间存在显著差异。使用这个基因集，我们能够建立一个新的模型来预测直肠癌对放射治疗的反应，准确率为82.4%。鉴别基因包括生长因子、凋亡、细胞增殖、信号转导或细胞粘附相关基因。在33个鉴别基因中，凋亡诱导剂（lumican，血小板反应蛋白2和半乳糖凝集素-1）在应答者中表现出较高的表达，而凋亡抑制剂（亲环素40和谷胱甘肽过氧化物酶）在无应答者中表现出较高的表达。本研究表明，基因表达谱可能是有用的，在预测放射治疗的反应，以建立一个个性化的定制治疗直肠癌的可能性。应答者和非应答者的全球表达谱可以为开发新的治疗靶点提供见解。
Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion-related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets.