Prediction of sensitivity of rectal cancer in response to preoperative radiotherapy and chemoradiotherapy by DNA microarray analysis-Anew strategy for individualized tailored therapy ofrectal cancer

DNA微阵列分析预测直肠癌对术前放化疗的敏感性——直肠癌个体化治疗新策略

• 批准号: 18390361
• 负责人: WATANABE Toshiaki
• 金额: $ 9.89万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390361/
• 关键词: Rectal Cancer; DNA Microarrav; Prediction of response; Radiotherapy; Chemo radiotheranv; 方射線療法

Local recurrence is one of the major forms of recurrence after surgery for rectal cancer. Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, in the clinical settings, the response to radiotherapy differs among individual tumors. Therefore, to select patients who respond to radiotherapy is very important to perform radiotherapy effectively. We aimed 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 … More 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%. Using the same strategy, we further performed a study to build a predictive model for chemoradiotherapy for rectal cancer. We examined a total of 15 patients who underwent preoperative chemoradiotherapy for rectal cancer. The patients underwent surgery after chemoradiotherapy using oral 5-FU(Fluorouracil) drugs. Response to chemoradiotherapy was determined by histological examination of surgically resected specimens as described above. By gene expression analysis, we could build a model which could predict the response to chemoradiotherapy with an accuracy of 100%. Although the number of examined patients is not large, these results suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy and chemoradiotherapy to establish an individualized tailored therapy for rectal cancer. Less

局部复发是直肠癌术后复发的主要形式之一。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，在临床环境中，对放射治疗的反应在个体肿瘤之间是不同的。因此，选择对放射治疗有反应的患者对于有效地进行放射治疗是非常重要的。我们的目的是确定一组可用于表征和预测直肠癌放射治疗反应的鉴别基因。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 ...更多信息 新的鉴别基因，其表达在应答者和非应答者之间显著不同。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%。使用相同的策略，我们进一步进行了一项研究，以建立直肠癌放化疗的预测模型。我们共检查了15例接受术前放化疗的直肠癌患者。患者在使用口服5-FU（氟尿嘧啶）药物进行放化疗后接受了手术。通过如上所述的手术切除标本的组织学检查确定对化学放射疗法的反应。通过基因表达分析，我们可以建立一个模型，可以预测化疗和放疗的反应，准确率为100%。虽然检查的患者数量并不多，但这些结果表明，基因表达谱可能有助于预测对放疗和放化疗的反应，以建立直肠癌的个性化定制治疗。少

项目成果

Weekly oxaliplatin and preoperative radiotherapy as a new neoadjuvant therapy for locally-advanced rectal cancer.

每周奥沙利铂和术前放疗作为局部晚期直肠癌的新辅助治疗。

• 发表时间: 2006
• 期刊: Annals of Oncology 17(7)
• 作者: Watanabe T;Kiyomatsu T;Kanazawa T;et al.
• 通讯作者: et al.

Surveillance colonoscopy should be conducted in patients with colorectal Shistosomiasis even after successful treatment of the disease.

即使在成功治疗该疾病后，也应对结直肠血吸虫病患者进行监测性结肠镜检查。

• 发表时间: 2006
• 期刊: Intemational Journal of Immunopathology and Pharmacology 19(1)
• 作者: Konishi T;Watanabe T;Shibahara J;et al.
• 通讯作者: et al.

Chronic colitis promotes tumor development.

慢性结肠炎促进肿瘤的发展。

• 发表时间: 2006
• 期刊: Oncology Reports 15(6)
• 作者: Shinozaki S;Watanabe T;Sato H;et al.
• 通讯作者: et al.

Site distribution of gastrointestinal carcinoids differs between races.

胃肠道类癌的部位分布因种族而异。

• 发表时间: 2006
• 期刊: Gut 55(7)
• 作者: Konishi T;Watanabe T;Muto T;et al.
• 通讯作者: et al.

Loss of Smad4 protein expression and 18qLOH as molecular markers indicating lymph node metastasis in colorectal cancer—a study matched for tumor depth and pathology

• DOI: 10.1002/jso.20896
• 发表时间: 2008
• 期刊: Journal of Surgical Oncology
• 影响因子: 2.5
• 作者: Toshiaki Tanaka;Toshiaki Watanabe;Y. Kazama;J. Tanaka;T. Kanazawa;S. Kazama;H. Nagawa