Establishment of cDNA array-based predictive diagnostics of cancer for personalized medicine

• Project/Area Number: 15390368
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: HOKKAIDO UNIVERSITY
• Principal Investigator: TADA Mitsuhiro Hokkaido Univ., Inst.Genet.Med., Asso.Prof., 遺伝子病制御研究所, 助教授 (10241316)
• Co-Investigator(Kenkyū-buntansha): KONDO Satoshi Hokkaido Univ., Grad.Sch.Med., Prof., 大学院・医学研究科, 教授 (30215454) ; MORIUCHI Tetsuya Hokkaido Univ., Inst.Genet.Med., Prof., 遺伝子病制御研究所, 教授 (20174394) ; HAMADA Jun-ichi Hokkaido Univ., Inst.Genet.Med., Asso.Prof., 遺伝子病制御研究所, 助教授 (50192703) ; 加藤 紘之 北海道大学, 大学院・医学研究科, 教授 (80002369)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥12,400,000 (Direct Cost: ¥12,400,000); Fiscal Year 2004: ¥5,800,000 (Direct Cost: ¥5,800,000); Fiscal Year 2003: ¥6,600,000 (Direct Cost: ¥6,600,000)
• Keywords: cDNA array data / expression profile / human cancer / malignant character / personalized medicine

Research Abstract

This project aimed to establish a predictive method of cDNA array-based prediction of malignant characters of cancers for personalized treatment for patients. We collected frozen cancer tissue samples surgically reseated in 31 hospitals in Hokkaido prefecture and analyzed the mRNA expression profiles with cDNA array analysis. By using of a novel computer algorithm which efficiently select features (gene expressions) that were significantly correlated with malignant characters of cancers, we explored functional significance of the gene expressions and established an effective method of personalization.
1)We could collect more than 5,800 cases of cancer samples and the pertinent clinicopathological data.
2)Among them, 600 cases were analyzed with cDNA array.
3)We developed a new method of feature subset selection utilizing k-nearest neighbor as an assessment function, a method of ensemble machine learning combining probabilistic neural networks.
4)By applying this method, we could effectively predict lymph node metastasis of colorectal cancers, lung cancers and esophageal cancers, short term survival of patients with pancreatic cancers, long-term survival of gastric caner patients, and perineural invasion of bile-duct cancers, histological malignancy of breast cancers and liver cancers. These have been reported in academic meetings and published in international journals.

Research Products

• [Journal Article] Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical strafication allows a high accuracy prediction of lymph node metastasis. (2005)
  • Author(s): Komuro K, et al.
  • Journal Title: Journal of Surgical Research 124 Pages: 216-224
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prediction of lymphatic invasion/lymph node metastasis, recurrence and survival in patients with gastric cancer by cDNA array-based expression profiling. (2005)
  • Author(s): Teramoto K, et al.
  • Journal Title: Journal of Surgical Research 124 Pages: 225-236
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Right and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis. (2005)
  • Author(s): Komuro K, Tada M, Tamoto E, Kawakami A, Matsunaga A, Teramoto K, Shindoh G, Takada M, Murakawa K, Kanai M, Kobayashi N, Fujiwara Y, Nishimura N, Hamada J-I, Ishizu A, Ikeda H, Kondo S, Katoh H, Moriuchi T, Yoshiki T
  • Journal Title: J Surg Res 124 Pages: 216-224
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiting. (2005)
  • Author(s): Teramoto K, Tada M, Tamoto E, Abe M, Kawakami A, Komuro K, Matsunaga A, Shindoh G, Takada M, Murakawa K, Kanai M, Kobayashi N, Fujiwara Y, Nishimura N, Shirata K, Takahishi T, Ishizu A, Ikeda H, Hamada J-I, Kondo S, Katoh H, Moriuchi T, Yoshiki T
  • Journal Title: J Surg Res 124 Pages: 225-236
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aberrant expression of HOX genes in human invasive breast carcinoma. (2005)
  • Author(s): Makiyama K, Hamada J, Takada M, Murakawa K, Takahashi Y, Tada M, Tamoto E, Shindo G, Matsunaga A, Teramoto K, Komuro K, Kondo S, Katoh H, Koike T, Moriuchi T
  • Journal Title: Oncol Rep 13 Pages: 673-679
  • NAID: 120002004281
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] p53-defective tumors with a functional apoptosome-mediated pathway : a new therapeutic target. (2005)
  • Author(s): Mashima T, Oh-hara T, Sato S, Mochizuki M, Sugimoto Y, Yamazaki K, Hamada J, Tada M, Moriuchi T, Ishikawa Y, Kato Y, Tomoda H, Yamori T, Tsuruo T
  • Journal Title: J Natl Cancer Inst 18 Pages: 765-777
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Altered expressions of HOX genes in human cutaneous malignant melanoma. (2005)
  • Author(s): Maeda K, Hamada J, Takahashi Y, Tada M, Yamamoto Y, Sugihara T, Moriuchi T
  • Journal Title: Int J Cancer 10 Pages: 436-441
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling. (2005)
  • Author(s): Teramoto K, et al.
  • Journal Title: Journal of Surgical Research in press
• [Journal Article] Right and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis. (2005)
  • Author(s): Komuro K, et al.
  • Journal Title: Journal of Surgical Research in press
• [Journal Article] Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system. (2004)
  • Author(s): Takahashi Y, et al.
  • Journal Title: Experimental Cell Research 293 Pages: 144-153
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gene-expression profile changes correlated with tumor progression and lymph node metastasis in esophageal cancer. (2004)
  • Author(s): Tamoto E, et al.
  • Journal Title: Clinical Cancer Research 10 Pages: 3629-3638
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data. (2004)
  • Author(s): Murakawa K, et al.
  • Journal Title: Journal of Surgical Research 122 Pages: 184-194
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer. (2004)
  • Author(s): Takada M, et al.
  • Journal Title: Journal of Surgical Research 122 Pages: 61-69
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system. (2004)
  • Author(s): Takahashi Y, Hamada J-I, Murakawa K, Takada M, Tada M, Nogami I, Hayashi N, Nakamori S, Monden M, Miyamoto M, Katoh H, Moriuchi T
  • Journal Title: Exp Cell Res 293 Pages: 144-153
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gene-expression profile changes correlated with tumor progression and lymph node metastasis in esophageal cancer. (2004)
  • Author(s): Tamoto E, Tada M, Murakawa K, Takada M, Shindo G, Teramoto K-I, Matsunaga A, Komuro K, Kanai M, Kawakami A, Fujiwara Y, Kobayashi N, Shirata K, Nishimura N, Okushiba S, Kondo S, Hamada J-I, Yoshiki T, Moriuchi T, Katoh H
  • Journal Title: Clin Cancer Res 10 Pages: 3629-3638
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of lymph node metastasis and perineural invasion of biliary tract cancer by selected features from cDNA array data. (2004)
  • Author(s): Murakawa K, Tada M, Takada M, Tamoto E, Shindoh Gs Teramoto K-I, Matsunaga A, Komuro K, Kanai M, Kawakami A, Fujiwara Y, Kobayashi N, Shirata K, Nishimura N, Okushiba S-I, Kondo S, Hamada J-I, Katoh H, Yoshiki T, Moriuchi T
  • Journal Title: J Surg Res 122 Pages: 184-194
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prediction of Lymph Node Metastasis by Analysis of Gene Expression Profiles in Non-small Cell Lung Cancer. (2004)
  • Author(s): Takada, M, Tada M, Tamoto E, Kawakami A, Murakawa K, Shindoh G, Teramoto K-I, Matsunaga A, Komuro K, Kanai M, Fujiwara Y, Shirata K, Nishimura N, Miyamoto M, Okushiba S-I, Kondo S, Hamada J-I, Katoh H, Yoshiki T, Moriuchi T
  • Journal Title: J Surg Res 122 Pages: 61-69
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Epigenetic silencing of E-and P-cadherin gene expression in human melanoma cell lines. (2004)
  • Author(s): Tsutsumida A, Hamada J, Tada M, Aoyama T, Furuuchi K, Kanai Y, Yamamoto Y, Sugihara T, Moriuchi T
  • Journal Title: Int J Oncol 25 Pages: 1415-1421
  • NAID: 120002004297
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 病理診断における分子生物学 (2004)
  • Author(s): 多田光宏, 守内哲也(分担執筆)
  • Publisher: 文光堂,東京
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tazawa H, et al.: "Infiltration of Neutrophils is Required for Acquisition of Metastatic Phenotype of Benign Murine Fibrosarcoma Cells"American Journal of Pathology. 163. 2221-2232 (2003)
• [Publications] Monti P, et al.: "Characterization of the p53 mutants ability to inhibit p73b transactivation using a yeast-based functional assay"Oncogene. 22. 5252-5260 (2003)
• [Publications] Yamada H, et al.: "Reconstructed β-catenin/TCF4 signaling in yeast applicable to functional evaluation of APC mutations"American Journal of Pathology. 163. 2201-2209 (2003)
• [Publications] Hirai A, et al.: "Expression of AIE-75 PDZ-domain Protein Induces G2/M Cell Cycle Arrest in Human Colorectal Adenocarcinoma SW480 Cells"Cancer Letters. (in press). (2004)
• [Publications] Takahashi Y, et al.: "Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system"Experimental Cell Research. 293. 144-153 (2004)
• [Publications] Tamoto E, et al.: "Gene-expression profile changes correlated with tumor progression and lymph node metastasis in esophageal cancer"Clinical Cancer Research. (in press). (2004)