Clinical application of gene expression signature as a predictor of recurrence in colorectal cancer

• Project/Area Number: 23591962
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: TAKEMASA Ichiro 大阪大学, 医学(系)研究科(研究院), 助教 (50379252)
• Co-Investigator(Kenkyū-buntansha): MIZUSHIMA Tunekazu 大阪大学, 附属病院消化器外, 講師 (00527707) ; IKEDA Masataka 独立行政法人国立病院機構大阪医療センター, 外科, 研究員 (80335356) ; YAMAMOTO Hirofumi 大阪大学, 附属病院消化器外, 准教授 (30322184) ; SEKIMOTO Mithugu 独立行政法人国立病院機構大阪医療センター, 外科, 研究員 (10273658)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 大腸癌 / 予後・治療応答性 / 予測診断 / 臨床応用 / パスウェイ / 大腸がん / 遺伝子発現プロファイル / 予後予測 / 個別化医療 / 予後診断用臨床チップ / 癌の多様性 / 薬剤感受性

Research Abstract

We have been attempting to stratify curatively resected colorectal cancer(CRC) into good or poor prognoses based on gene expression signatures.Using the clinical DNA chip,we attempted to select discriminator genes,with the 150 retrospective CRC sample set,resulting 55 markers.We then applied the discriminator set to the second,150 CRC samples set in a prospective sample set for predictive accuracy and prognostic validity.Kaplan-Meyer analysis showed a significant difference between the"good signature group(low-risk)"and the "poor signature group (high risk)" (Log-rank p equal 0.0019).The multivariate Cox analyses showed the significant parameters to predict the prognosis with a hazard ratio of 3.5(95 persent confidence interval, 0.12-0.67 p=0.004). this personalized prognosis is crucial with CRC patients, the predictive performance may deserve serious consideration for possible application to clinic.

Research Products

• [Journal Article] Ephrin-A1 mRNA is associated with poor prognosis of colorectal cancer (2013)
  • Author(s): Yamamoto H., Tei M., Uemura M., Takemasa I., Uemura Y., Murata K., Fukunaga M., Ohue M., Ohnishi T., Ikeda K., Kato T., Okamura S., Ikenaga M., Haraguchi N., Nishimura J., Mizushima T., Mimori K., Doki Y., Mori M.
  • Journal Title: Int J Oncol Pages: 549-555
• [Journal Article] Depletion of JARID1B induces cellular senescence in human colorectal cancer (2013)
  • Author(s): Ohta K., Haraguchi N., Kano Y., Kagawa Y., Konno M., Nishikawa S., Hamabe A., Hasegawa S., Ogawa H., Fukusumi T., Uemura M., Nishimura J., Hata T., Takemasa I., Mizushima T., Noguchi Y., Ozaki M., Kudo T., Sakai D., Satoh T., Fukami M., Ishii M., Yamamoto H., Doki Y., Mori M., Ishii H.
  • Journal Title: Int J Oncol Pages: 1212-1218
• [Journal Article] Metabolic system alterations in pancreatic cancer patient serum : potential for early detection (2013)
  • Author(s): Ritchie SA., Akita H., Takemasa I., Eguchi H., Pastural E., Nagano H., Monden M., Doki Y., Mori M., Jin W., Sajobi TT., Jayasinghe D., Chitou B., Yamazaki Y., White T., Goodenowe DB.
  • Journal Title: BMC Cancer
• [Journal Article] An Impact of Epigenetic Approaches Targeting JARID1B to Modulate Malignant Behaviors of Gastrointestinal Cancer (2013)
  • Author(s): Yamamoto H.
  • Journal Title: Int J Oncol Volume: 42 Pages: 549-555
• [Journal Article] Depletion of JARID1B induces cellular senescence in human colorectal cancer. (2013)
  • Author(s): Ohta K.
  • Journal Title: Int J Oncol Volume: 42 Pages: 1212-1218
• [Journal Article] Metabolic system alterations in pancreatic cancer patient serum: potential for early detection. (2013)
  • Author(s): Ritchie SA.
  • Journal Title: BMC Cancer Volume: 13 Issue: 1 Pages: 416-416
  • DOI: 10.1186/1471-2407-13-416
• [Journal Article] Potential biological insights revealed by an integrated assessment of proteomic and transcriptomic data in human colorectal cancer. (2012)
  • Author(s): Takemasa I.
  • Journal Title: Int J Oncol Volume: 2 Pages: 551-559
  • Peer Reviewed
• [Journal Article] Heterogeneity of colorectal cancers extraction of discriminator gene signatures for parsonalized of prognosis. (2011)
  • Author(s): Miyake M
  • Journal Title: Int J Oncol Volume: 39 Pages: 781-789
  • Peer Reviewed
• [Presentation] O-67-3膵癌診断のためのメタボロミクス技術を用いた新規バイオマーカーの探索(一般演題) (2013)
  • Author(s): 秋田裕史、永野浩昭、竹政伊知朗、濱直樹、和田浩志、川本弘一、小林省吾、江口英利、森正樹、土岐祐一郎
  • Organizer: 第68回日本消化器外科学会総会
  • Place of Presentation: 宮崎
• [Presentation] An Impact of Epigenetic Approaches Targeting JARID1B to Modulate Malignant Behaviors of Gastrointestinal Cancer (Minisymposium) (2013)
  • Author(s): Ohta K., Kano Y., Konno M., Kagawa Y., Nishikawa S., Hasegawa S., Fukusumi T., Ogawa H., Hamabe A., Satoh T., Haraguchi N., Yamamoto H., Doki Y., Mori M., Ishii H.
  • Organizer: American Association for Cancer Research(AACR) Annual Meeting 2013
  • Place of Presentation: Washington DC, USA
• [Presentation] An Impact of Epigenetic Approaches Targeting JARID1B to Modulate Malignant Behaviors of Gastrointestinal Cancer (2013)
  • Author(s): Kano Y., Konno M., Kagawa Y., Nishikawa S., Hasegawa S., Fukusumi T., Ogawa H., Hamabe A., Satoh T., Haraguchi N., Yamamoto H., Doki Y., Mori M., Ishii H.
  • Organizer: American Association for Cancer Research(AACR) Annual Meeting 2013
  • Place of Presentation: Washington DC, USA
• [Presentation] O-67-3 膵癌診断のためのメタボロミクス技術を用いた新規バイオマーカーの探索 (2013)
  • Author(s): 秋田裕史
  • Organizer: 第68回 日本消化器外科学会総会
  • Place of Presentation: 宮崎
• [Presentation] OSNA法を用いた新たな大腸癌リンパ節転移検査への可能性 (2011)
  • Author(s): 山本浩文
  • Organizer: 第66回 日本消化器外科学会
  • Place of Presentation: 名古屋
• [Presentation] 大腸癌リンパ節転移におけるOSNA法を用いた新たな分子生物学的検査法の意義 (2011)
  • Author(s): 宮崎進
  • Organizer: 第111回 日本外科学会
  • Place of Presentation: 紙上開催
• [Presentation] ヒストン脱メチル化酵素JMJD1Aの大腸癌悪性度とEMTへの関与 (2011)
  • Author(s): 宮崎進
  • Organizer: 第66回 日本消化器外科学会
  • Place of Presentation: 名古屋