マイクロアレイを用いた大腸癌術後肝転移の予測および新規肝転移関連遺伝子の検討

• 研究課題/領域番号: 19591565
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 消化器外科学
• 研究機関: 帝京大学
• 研究代表者: 松田 圭二 帝京大学, 医学部, 准教授 (90302728)
• 研究分担者: 渡邉 聡明 帝京大学, 医学部, 教授 (80210920) ; 野澤 慶次郎 帝京大学, 医学部, 助教 (90317686) ; 飯沼 久恵 帝京大学, 医学部, 講師 (30147102)
• 連携研究者: 渡邉 聡明 帝京大学, 医学部, 教授 (80210920) ; 野澤 慶次郎 帝京大学, 医学部, 助教 (90317686) ; 飯沼 久恵 帝京大学, 医学部, 講師 (30147102)
• 研究期間 (年度): 2007 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円); 2008年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円); 2007年度: 2,340千円 (直接経費: 1,800千円、間接経費: 540千円)
• キーワード: 大腸癌 / 肝転移 / 遺伝子発現解析 / マイクロアレイ / テーラーメイド治療

研究概要

外科的切除が行われた、80例の肝転移例をtrainiug setして約54,000種類の遺伝子発現解析を行い、肝転移の予測式を作成した。この結果、予測精度72.5%で肝転移の有無の予想が可能であった.次ぎに独立した20例の解析を行い、予測式の精度を確認した
結果、70.0%の精度で肝転移の予測が可能であった。本予測式により、大腸癌術後の肝転移再発の高リスク例の選別ができる可能性が示唆された。

研究成果

• [雑誌論文] Gene expression signature for recurrence in stage III colorectal cancers (2009)
  • 著者名/発表者名: Watanabe T, Kobunai T, Sakamoto E, Yamamoto Y, Konishi T, Horiuchi A, Shimada R, Oka T, Nagawa H.
  • 雑誌名: Cancer 115(2) ページ: 283-92
  • 査読あり
• [雑誌論文] Gene expression signature for recurrence in stage III colorectal cancers. (2009)
  • 著者名/発表者名: Watanabe T, Kobunai T, Sakamoto E, et al.
  • 雑誌名: Cancer 115 ページ: 283-92
  • 査読あり
• [雑誌論文] Chemoradiotherapy and adjuvant chemotherapy for rectal cancer (2008)
  • 著者名/発表者名: Watanabe T.
  • 雑誌名: Int J Clin Oncol 13(6) ページ: 488-97
  • NAID: 10023919933
  • 査読あり
• [雑誌論文] Recent advances in chemotherapy and chemoradiotherapy for gastrointestinal tract cancers (2008)
  • 著者名/発表者名: Watanabe T.
  • 雑誌名: Int J Clin Oncol 13(6) ページ: 472-3
  • NAID: 10023919813
  • 査読あり
• [雑誌論文] Predicting clinical outcome to 5-Fluorouracil-based chemotherapy for colon cancer patients : is it the CpG island methylator phenotype? (2008)
  • 著者名/発表者名: Iacopetta B, Kawakami K. Watanabe T.
  • 雑誌名: Int J Clin Oncol 13 (6) ページ: 498-503
  • 査読あり
• [雑誌論文] Intraoperative colonoscopy for stapled anastomosis in colorectal surgery (2008)
  • 著者名/発表者名: Ishihara S, Watanabe T, Nagawa H.
  • 雑誌名: Surg Today 38 (11) ページ: 1063-5
  • NAID: 10024429407
  • 査読あり
• [雑誌論文] Telomerase activity of blood samples and recurrence of colorectal cancer (2008)
  • 著者名/発表者名: Ohnishi T. Watanabe T. Nozawa H,Kitayama J, Nagawa H.
  • 雑誌名: Hepatogastroenterology 55(86-87) ページ: 1513-8
  • 査読あり
• [雑誌論文] Lateral pelvic lymph node dissection or chemoradiotherapy : which is the procedure of choice to reduce local recurrence rate in lower rectal cancer? (2008)
  • 著者名/発表者名: Watanabe T, Niatsuda K, Nozawa K, Kobunai T.
  • 雑誌名: Ann Surg 248 (2) ページ: 342-3
  • 査読あり
• [雑誌論文] Survival in microsatellite-unstable colorectal cancer (2008)
  • 著者名/発表者名: Watanabe T, Yamamoto Y. Yamada H.Hayama T, Aoyagi Y, Nakamura K, Shibuya H. Kobunai T.
  • 雑誌名: Clin Cancer Res 14 (8) ページ: 2516-7
  • 査読あり
• [雑誌論文] Prognostic value of 5-fluorouracil metabolic enzyme genes in Dukes' stage B and C colorectal cancer patients treated with oral 5-fluorouracil-based adjuvant chemotherapy (2008)
  • 著者名/発表者名: Yamada H, linuma H. Watanabe T.
  • 雑誌名: Oncol Rep 19(3) ページ: 729-35
  • 査読あり
• [雑誌論文] Endoscopic and chromoendoscopic atlas featuring dysplastic lesionsin surveillance colonoscopy for patients with long-standing ulcerative colitis (2008)
  • 著者名/発表者名: Matsumoto T, Iwao Y, Igarashi M,Watanabe K. Otsuka K, Watanabe T, Iizuka B, H i da N. Sada M, Chiba T.Kudo SE, Oshitani N, Nagawa H, Ajioka Y, Hibi T.
  • 雑誌名: Inf lam Bowel Dis 14(2) ページ: 259-64
  • 査読あり
• [雑誌論文] Loss of Smad4 protein expression and 180LOH as molecular markers indicating lymph node metastasis in colorectal cancer-a study matched for tumor depth and pathology (2008)
  • 著者名/発表者名: Tanaka T, Watanabe T, Kazama Y. Tanaka J, Kanazawa T, Kazama S, Nagawa H.
  • 雑誌名: J Surg Oncol 97 (1) ページ: 69-73
  • 査読あり
• [雑誌論文] Lateral pelvic lymph node dissection or chemoradiotherapy : which is the procedure of choice to reduce local recurrence rate in lower rectal cancer? (2008)
  • 著者名/発表者名: Watanabe T, Matsuda K, Nozawa K, et al.
  • 雑誌名: Annals of Surgery 248 ページ: 342-3
  • 査読あり
• [雑誌論文] Survival in microsatellite-unstable colorectal cancer. (2008)
  • 著者名/発表者名: Watanabe T, Yamamoto Y, Yamada H, et al.
  • 雑誌名: Clinical Cancer Research 14 ページ: 2516-7
  • 査読あり
• [雑誌論文] Chemoradiotherapy and adjuvant chemotherapy for rectalcancer. (2008)
  • 著者名/発表者名: Watanabe T.
  • 雑誌名: International Journal of Clinical Oncology 13(6) ページ: 488-97
  • 査読あり
• [雑誌論文] Recent advances in chemotherapy and chemoradiotherapy for gastrointestinal tract cancers. (2008)
  • 著者名/発表者名: Watanabe T.
  • 雑誌名: International Journal of Clinical Oncology 13 ページ: 472-3
  • NAID: 10023919813
  • 査読あり
• [雑誌論文] Predicting clinical outcome to 5-Fluorouracil-based chemotherapy for colon cancer patients : is it the CpG island methylator phenotype? (2008)
  • 著者名/発表者名: Iacopetta B, Kawakami K, Watanabe T
  • 雑誌名: International Journal of Clinical Oncology 13 ページ: 498-503
  • 査読あり
• [雑誌論文] Intraoperative colonoscopy for stapled anastomosis in colorectal surgery. (2008)
  • 著者名/発表者名: Ishihara S, Watanabe T, Nagawa H.
  • 雑誌名: Surgery Today 38 ページ: 1063-5
  • NAID: 10024429407
  • 査読あり
• [雑誌論文] Telomerase activity of blood saraples and recurrence ofcolorectal cancer. (2008)
  • 著者名/発表者名: Ohnishi T, Watanabe T, Nozawa H, et al.
  • 雑誌名: Hepatogastroenterology 55 ページ: 1513-8
  • 査読あり
• [雑誌論文] Loss of Smad4 protein expression and 18qLOH as molecular markers in dicating lymph node metastasis in colorectal cancer-a study matched for tumor depth and pathology. (2008)
  • 著者名/発表者名: Tanaka T, Watanabe T, Kazama Y, et. al.
  • 雑誌名: J Surg Oncol 97(1) ページ: 69-73
  • 査読あり
• [雑誌論文] Prognostic value of 5-fluorouracil metabolic enzyme genes in Dukes' stage B and C colorectal cancer patients treated with oral 5-fluorouracil-based adjuvant chemotherapy (2008)
  • 著者名/発表者名: Yamada H, Iinuma H, Watanabe T.
  • 雑誌名: Oncol Rep 19(3) ページ: 729-35
  • 査読あり
• [雑誌論文] Left-sided microsatellite unstable colorectal cancers show less frequent methylation of hMLH1 and CpG island methylator phenotype than right-sided ones (2007)
  • 著者名/発表者名: Tanaka J, Watanabe T, Kanazawa T, Tada T, Kazama Y, Tanaka T, Nagawa H.
  • 雑誌名: J Surg Oncol 96 (7) ページ: 611-8
  • 査読あり
• [雑誌論文] The 4-portai technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer : comparison between the 2-portal and the 4-portal techniques (2007)
  • 著者名/発表者名: Kiyomalsu T, Watanabe T, Muto T, Nagawa H.
  • 雑誌名: Am J Surg 194 (4) ページ: 542-8
  • 査読あり
• [雑誌論文] I ; Surgical Research Group, the Research Committee of Inflammatory Bowel Disease, Ministry of Health, Labour and Welfare of Japan. Pouchitis atlas for objective endoscopic diagnosis (2007)
  • 著者名/発表者名: Fukushima K, Fujii H, Yamamura T,Sugi to A, Kameoka S, Nagawa H, Futami K, Watanabe T, Hatakeyama K, Sawada T, Yoshioka K, Kusunoki M, Konishi F, Watanabe M, Takahashi K, Ogawa H, Funayama Y, Hibi T, Sasaki
  • 雑誌名: J Gastroenterol 42 (10) ページ: 799-806
  • 査読あり
• [雑誌論文] Rapid genetic diagnosis with transcription-reverse transcription concerted reaction system for peritoneal recurrence and survival in colorectal cancer patients (2007)
  • 著者名/発表者名: Hayama T, Iinuma H, Watanabe T.
  • 雑誌名: Oncol Rep 18 (41) ページ: 779-84
  • 査読あり
• [雑誌論文] Basic fibroblast growth factor enema improves experimental colitis in rats (2007)
  • 著者名/発表者名: Kojima T, Watanabe T, Nagawa H.
  • 雑誌名: Hepatogastroenterology 54 (77) ページ: 1373-7
  • 査読あり
• [雑誌論文] Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human colorectal cancer (2007)
  • 著者名/発表者名: Nozawa H, Watanabe T, Nagawa H.
  • 雑誌名: Cancer Lett 251 (1) ページ: 105-13
  • 査読あり
• [雑誌論文] Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum : relationship to clinicopathological features (2007)
  • 著者名/発表者名: Kazama Y, Watanabe T, Kanazawa T,Tanaka J, Tanaka T, Nagawa H.
  • 雑誌名: J Clin Pathol 60 (6) ページ: 701-4
  • 査読あり
• [雑誌論文] Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray. (2007)
  • 著者名/発表者名: Watanabe T, Kobunai T, Toda E, et. al.
  • 雑誌名: Clin Cancer Res 13(2) ページ: 415-420
  • 査読あり
• [雑誌論文] Rapid genetic diagnosis with transcription-reverse transcription concerted reaction system for peritoneal recurrence and survival in colorectal cancer patients (2007)
  • 著者名/発表者名: Hayama T, Iinuma H, Watanabe T.
  • 雑誌名: Oncol Rep 18(4) ページ: 779-784
  • 査読あり
• [雑誌論文] Vascular endothelial growth factor-C(VEGF-C)is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer (2007)
  • 著者名/発表者名: Kazama S, Watanabe T, Kanazawa T, et. al.
  • 雑誌名: Hepatogastroenterology 54(73) ページ: 71-76
  • 査読あり
• [雑誌論文] Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum:relationship to clinicopathological features. (2007)
  • 著者名/発表者名: Kazama Y, Watanabe T, Kanazawa T, et. al.
  • 雑誌名: J Clin Pathol 60(6) ページ: 701-4
  • 査読あり
• [雑誌論文] The 4-portal technique decreases adverse effects in preoperative radioth erapy for advanced rectal cancer:comparison between the 2-portal and the 4-portal techniques (2007)
  • 著者名/発表者名: Kiyomatsu T, Watanabe T, Muto T, et. al.
  • 雑誌名: Am J Surg 194(4) ページ: 542-8
  • 査読あり
• [雑誌論文] Perioperative radiation for rectal cancer and sexual dysfunction after TME:cause and effect? (2007)
  • 著者名/発表者名: Konishi T, Watanabe T, Kiyomatsu T, et. al.
  • 雑誌名: Ann Surg 245(1) ページ: 155-155
  • 査読あり
• [雑誌論文] Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human colorectal cancer. (2007)
  • 著者名/発表者名: Nozawa H, Watanabe T, Nagawa H.
  • 雑誌名: Cancer Lett 251(1) ページ: 105-13
  • 査読あり
• [雑誌論文] Left-Sided microsatellite unstable colorectal cancers show less fiequent methylation of hMLH1 and CpG island methylator phenotype than right-sided ones. (2007)
  • 著者名/発表者名: Tanaka J, Watanabe T, Kanazawa T, et. al.
  • 雑誌名: J Surg Oncol 96(7) ページ: 611-8
  • 査読あり
• [雑誌論文] Unusual Pressure-induced Rupture of Colonic Volvulus in a Patient treated with Chronic Corticostcroid Therapy
  • 著者名/発表者名: Tanaka T, Watanabe T, Konishi T,Shibahara J, Kanazawa T, Kazama S, Nagawa H.
  • 雑誌名: Acta Gastroenterol Belg (in press)
  • 査読あり
• [雑誌論文] Chromosome 18q deletion as a novel molecular predictor for colorectal cancer with simultaneous hepatic metastasis
  • 著者名/発表者名: Tanaka T, Watanabe T, Kitayama J, Kazama Y, Tanaka J, Kanazawa T, Kazama S, Nagawa H.
  • 雑誌名: Diagn Mol Pathol (in press)
  • 査読あり
• [雑誌論文] Unusual Pressure-induced Rupture of Colonic Volvulus ina Patient treated with Chronic Corticosteroid Therapy.
  • 著者名/発表者名: Tanaka T, Watanabe T, Konishi T, et al.
  • 雑誌名: Acta Gastro-enterologica Belgica in press
  • 査読あり
• [雑誌論文] Chromosome 18q deletion as a novel molecular predictorfor colorectal cancer with simultaneous hepatic metastasis.
  • 著者名/発表者名: Tanaka T, Watanabe T, Kitayama J, et al.
  • 雑誌名: Diagnostic molecular pathology in press
  • 査読あり