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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 大腸癌 / 予後・治療応答性 / 予測診断 / 臨床応用 / パスウェイ

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 Pages: 未定
• [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
  • Year and Date: 20130700
• [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
  • Year and Date: 20130400