Prediction of Response to Molecular-targeting agents in colorectal cancer By Gene expression Analysis

• Project/Area Number: 24659620
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: WATANABE TOSHIAKI 東京大学, 医学部附属病院, 教授 (80210920)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大腸癌 / DNAマイクロアレイ / 化学療法 / 遺伝子発現 / 血行性転移 / 遺伝子発現解析 / マイクロアレイ / テーラーメイド治療

Research Abstract

Based on the gene expression of colorectal cancers, we aimed to build a predictive model for response to chemotherapy based on molecular target agent (bevacizumab). Using 41 samples, we examined gene expression by microarray, then validated them by RT-PCR method. We finally selected 3- and 2-gene sets and made 2-gene and 3-gene predictive models. The accuracy rate of prediction was 73.2 %(3-gene model) and 75.6%(2-gene model). We also examined the correlations of these genes with individual drug responses on tumor cell lines deposited on public database.

Research Products

• [Journal Article] Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes (2014)
  • Author(s): Watanabe T, Kobunai T, Akiyoshi T, Matsuda K, Ishihara S, Nozawa K
  • Journal Title: Dis Colon Rectum Volume: 57(1) Pages: 23-31
  • Peer Reviewed
• [Journal Article] Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes. (2014)
  • Author(s): Watanabe T, Kobunai T, Akiyoshi T, Matsuda K, Ishihara S, Nozawa K.
  • Journal Title: Dis Colon Rectum. Volume: 57(1) Issue: 1 Pages: 23-31
  • DOI: 10.1097/01.dcr.0000437688.33795.9d
  • Peer Reviewed
• [Journal Article] Selective Lateral Pelvic Lymph Node Dissection in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy Based on Pretreatment Imaging. (2014)
  • Author(s): Akiyoshi T, Ueno M, Matsueda K, Konishi T, Fujimoto Y, Nagayama S, Fukunaga Y, Unno T, Kano A, Kuroyanagi H, Oya M, Yamaguchi T, Watanabe T, Muto T.
  • Journal Title: Ann Surg Oncol Volume: 21(1) Issue: 1 Pages: 189-96
  • DOI: 10.1245/s10434-013-3216-y
  • Peer Reviewed
• [Journal Article] Intraperitoneal administration of cisplatin via an in situ cross-linkable hyaluronic acid-based hydrogel for peritoneal dissemination of gastric cancer. (2014)
  • Author(s): Emoto S, Yamaguchi H, Kamei T, Ishigami H, Suhara T, Suzuki Y, Ito T, Kitayama J, Watanabe T.
  • Journal Title: Surgery Today Volume: 44 Issue: 5 Pages: 919-26
  • DOI: 10.1007/s00595-013-0674-6
  • Peer Reviewed / Open Access
• [Journal Article] Colorectal cancer and hypercoagulability. (2014)
  • Author(s): Kawai K, Watanabe T.
  • Journal Title: Surg Today Volume: 44(5) Issue: 5 Pages: 797-803
  • DOI: 10.1007/s00595-013-0606-5
  • Peer Reviewed
• [Journal Article] Flow cytometric quantification of intraperitoneal free tumor cells in patients with peritoneal metastasis. (2014)
  • Author(s): Kitayama J, Emoto S, Yamaguchi H, Ishigami H, Kamei T, Yamashita H, Seto Y, Matsuzaki K, Watanabe T.
  • Journal Title: Cytometry B Clin Cytom Volume: 86 Issue: 1 Pages: 56-62
  • DOI: 10.1002/cyto.b.21126
  • Peer Reviewed / Open Access
• [Journal Article] CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment. (2014)
  • Author(s): Kitayama J
  • Journal Title: PLoS One Volume: 21;9(1) Issue: 1 Pages: e86516-e86516
  • DOI: 10.1371/journal.pone.0086516
  • Peer Reviewed / Open Access
• [Journal Article] Salvage gastrectomy after intravenous and intraperitoneal paclitaxel (PTX) administration with oral S-1 for peritoneal dissemination of advanced gastric cancer with malignant ascites. (2014)
  • Author(s): Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T.
  • Journal Title: Ann Surg Oncol. Volume: 21 Issue: 2 Pages: 539-46
  • DOI: 10.1245/s10434-013-3208-y
  • Peer Reviewed / Open Access
• [Journal Article] Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis. (2014)
  • Author(s): Kobayashi H, Kotake K, Funahashi K, Hase K, Hirata K, Iiai T, Kameoka S, Kanemitsu Y, Maeda K, Murata A, Ohue M, Shirouzu K, Takahashi K, Watanabe T, Yano H, Yatsuoka T, Hashiguchi Y, Sugihara K
  • Journal Title: J Gastroenterol. Volume: 49(4) Issue: 4 Pages: 646-654
  • DOI: 10.1007/s00535-013-0820-3
  • Peer Reviewed
• [Journal Article] Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients. (2014)
  • Author(s): Tada N, Tsuno NH, Kawai K, Murono K, Nirei T, Ishihara S, Sunami E, Kitayama J, Watanabe T.
  • Journal Title: Oncol Rep Volume: 31 Issue: 1 Pages: 463-71
  • DOI: 10.3892/or.2013.2857
  • Peer Reviewed / Open Access
• [Journal Article] Salvage Gastrectomy After Intravenous and Intraperitoneal Paclitaxel (PTX) Administration with Oral S-1 for Peritoneal Dissemination of Advanced Gastric Cancer with Malignant Ascites (2013)
  • Author(s): Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T
  • Journal Title: Annals of Surgical Volume: 21(2) Pages: 539-46
  • Peer Reviewed
• [Journal Article] A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis (2013)
  • Author(s): Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T
  • Journal Title: Cancer Volume: 15;119(18) Pages: 3354-8
  • Peer Reviewed
• [Journal Article] KRAS Mutational Status in Japanese Patients with Colorectal Cancer : Results from a Nationwide, Multicenter, Cross-sectional Study (2013)
  • Author(s): Watanabe T, Yoshino T, Uetake H, Yamazaki K, Ishiguro M, Kurokawa T, Saijo N, Ohashi Y, Sugihara K
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 43(7) Pages: 706-12
  • Peer Reviewed
• [Journal Article] Thrombocytosis before pre-operative chemoradiotherapy predicts poor response and shorter local recurrence-free survival in rectal cancer. (2013)
  • Author(s): Kawai K.
  • Journal Title: Int J Colorectal Dis Volume: 28(4):527 Issue: 4 Pages: 527-35
  • DOI: 10.1007/s00384-012-1594-4
  • Peer Reviewed
• [Journal Article] KRAS Mutational Status in Japanese Patients with Colorectal Cancer: Results from a Nationwide, Multicenter, Cross-sectional Study. (2013)
  • Author(s): Watanabe T, Yoshino T, Uetake H, Yamazaki K, Ishiguro M, Kurokawa T, Saijo N, Ohashi Y, Sugihara K.
  • Journal Title: Jpn J Clin Oncol Volume: 43(7) Issue: 7 Pages: 706-12
  • DOI: 10.1093/jjco/hyt062
  • Peer Reviewed
• [Journal Article] A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis. (2013)
  • Author(s): Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T.
  • Journal Title: Cancer. Volume: 119 Issue: 18 Pages: 3354-8
  • DOI: 10.1002/cncr.28204
  • Peer Reviewed
• [Journal Article] Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer. (2013)
  • Author(s): Murono K, Kitayama J, Tsuno NH, Nozawa H, Kawai K, Sunami E, Akahane M, Watanabe T.
  • Journal Title: Int J Colorectal Dis Volume: 28(8) Issue: 8 Pages: 1065-72
  • DOI: 10.1007/s00384-013-1656-2
  • Peer Reviewed
• [Journal Article] Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy. (2013)
  • Author(s): Ishihara S, Watanabe T, Fukushima Y, Akahane T, Horiuchi A, Shimada R, Nakamura K, Hayama T, Yamada H, Nozawa K, Matsuda K, Hashiguchi Y.
  • Journal Title: Tech Coloproctol Volume: 18(3) Issue: 3 Pages: 247-55
  • DOI: 10.1007/s10151-013-1048-1
  • Peer Reviewed
• [Journal Article] Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition. (2013)
  • Author(s): Hongo K, Tsuno NH, Kawai K, Sasaki K, Kaneko M, Hiyoshi M, Murono K, Tada N, Nirei T, Sunami E, Takahashi K, Nagawa H, Kitayama J, Watanabe T.
  • Journal Title: J Surg Res Volume: 182(1) Issue: 1 Pages: 75-84
  • DOI: 10.1016/j.jss.2012.08.034
  • Peer Reviewed
• [Journal Article] Recent approaches to identifying biomarkers for high-risk stage II colon cancer (2012)
  • Author(s): Akiyoshi T, Kobunai T, Watanabe T
  • Journal Title: Surg Today Volume: 42(11) Pages: 1037-45
  • NAID: 10031120764
  • Peer Reviewed
• [Journal Article] Predicting the response to preoperative radiation or chemoradiation by a microarray analysis of the gene expression profiles in rectal cancer (2012)
  • Author(s): Akiyoshi T, Kobunai T, Watanabe T
  • Journal Title: Surg Today Volume: 42(8) Pages: 713-9
  • NAID: 10030948879
  • Peer Reviewed
• [Journal Article] Chromosomal instability (CIN) phenotype, CIN high or CIN low, predicts survival for colorectal cancer (2012)
  • Author(s): Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, Yamada H, Hayama T, Inoue E, Tamura J, Iinuma H, Akiyoshi T, Muto T
  • Journal Title: J Clin Oncol Volume: 20;30(18) Pages: 2256-64
  • Peer Reviewed
• [Journal Article] Chromosomal Instability (CIN) Phenotype, CIN High or CIN Low, Predicts Survival for Colorectal Cancer (2012)
  • Author(s): Watanabe T, Iinuma H, et al
  • Journal Title: J Clin Oncol Volume: 30(in press) Issue: 18 Pages: 2256-64
  • DOI: 10.1200/jco.2011.38.6490
  • Peer Reviewed
• [Journal Article] Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes' stage of colorectal cancer patients (2012)
  • Author(s): Horiuchi A, Iinuma H, et al
  • Journal Title: Oncol Rep Volume: 27 Pages: 1384-92
  • DOI: 10.3892/or.2012.1648
  • Peer Reviewed
• [Journal Article] Predicting the response to preoperative radiation or chemoradiation by a microarray analysis of the gene expression profiles in rectal cancer. (2012)
  • Author(s): Akiyoshi T, Kobunai T, Watanabe T.
  • Journal Title: Surgery Today Volume: 42 Issue: 8 Pages: 713-719
  • DOI: 10.1007/s00595-012-0223-8
  • NAID: 10030948879
  • Peer Reviewed
• [Journal Article] Recent approaches to identifying biomarkers for high-risk stage II colon cancer. (2012)
  • Author(s): Akiyoshi T, Kobinai T, Watanabe T
  • Journal Title: Surgery Today Volume: 42 Issue: 11 Pages: 1037-45
  • DOI: 10.1007/s00595-012-0324-4
  • NAID: 10031120764
  • Peer Reviewed
• [Journal Article] Polyp surveillance after surgery for colorectal cancer. (2012)
  • Author(s): Kawai K, Sunami E, Tsuno NH, Kitayama J, Watanabe T.
  • Journal Title: International journal of colorectal disease Volume: 27 Pages: 1087-93
  • Peer Reviewed
• [Journal Article] Japanese Society for Cancer of the Colon and Rectum. "Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease?" (2012)
  • Author(s): Akiyoshi T, Watanabe T, Miyata S, Kotake K, Muto T, Sugihara K
  • Journal Title: Ann Surg Volume: 255(6) Issue: 6 Pages: 1129-1134
  • DOI: 10.1097/sla.0b013e3182565d9d
  • Peer Reviewed
• [Journal Article] Impact of chronic kidney disease on outcomes of surgical resection for primary colorectal cancer: a retrospective cohort review. (2012)
  • Author(s): Nozawa H, Kitayama J, Sunami E, Watanabe T.
  • Journal Title: Diseases of the Colon and Rectum Volume: 55 Issue: 9 Pages: 948-56
  • DOI: 10.1097/dcr.0b013e3182600db7
  • Peer Reviewed