Molecular Genetics of the Heterogeneiety of Gastrointestinal Cancer in association of cancer stem cells.

• Project/Area Number: 18390367
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: INOUE Hiroshi Kyushu University, Medical Institute of Bioregulation, Department of Molecular and Cellular Biology, Associate Professor (90203249)
• Co-Investigator(Kenkyū-buntansha): MIMORI Koshi Kyushu University, Medical Insttitute of Bioregulation, Department of Molecular and Cellular Biology, Research Associate (50322748) ; TANAKA Fumiaki Kyushu University, Hospital, Department of Molecular and Cellular Biology, Research Associate (30332836) ; MORI Masaki Kyushu University, Medical Insttitute of Bioregulation, Medical Insttitute of Bioregulation, Department of Molecular and Cellular Biology, Professor (70190999)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥17,620,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: Cancer / Heterogeneity / DNA microarray / LMD / Gastric cancer / Hepatocellular carcinoma / Laser pressure cell transfer method / Genome array / CD49 / 抗癌剤耐性 / SP

Research Abstract

Purpose
To investigate the genetic base of the heterogeneity of the digestive cancer, two approaches such as 1) DNA microarray analysis combined with laser microdissection for the gene expression of the digestive tract carcinoma and 2) cancer stem cell survey have been conducted.
Material and method
Cell line and clinically resected tumor specimens were used for the analysis. Human 44k-DNA microarray were purchased from “Agilent technology" and microarray analysis were performed according to the company's instruction. In addition, genomic microarray were performed for 10 cases of esophageal cancer and 5 cased of heptocellular carcinoma.
Results
1) Early staged cancer shows no definitive different expression profile from various parts of the tumor, however, in advance staged cancer, a definitive difference of the profile was observed among the portions of the tumor, in particular, superficial luminal parts and deeper invasive portions. 2) Expression profiles differ in cases with different histological types. 3) Genomic alteration and simultaneous mRNA expression changes were observed in accordance with the histological development of the tumor. In heptocellular carcinoma, peripheral portion of the tumor shows very faint alteration in both mRNA and genomics. However, in the central portion that reciprocally later developed, histologically showed more aggressive pattern and also manifested very variable alterations in both mRNA and genomics.
Discussion
DNA microarray analysis combined with laser microdissection for the gene expression as well as genomic alteration had very powerful potential for the analysis of histologically complexed tumor. More detailed study will clarify the perplexed nature of the human carcinogenesis.

Research Products

• [Journal Article] Clinical Significance of BMP7 in Human Colorectal Cancer (2008)
  • Author(s): Motoyama, K, 他
  • Journal Title: Ann Surg Oncol (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Efficient identification of a novel cancer/testis antigen forimmunotherapy using three-step microarray analysis (2008)
  • Author(s): Yokoe, T., 他
  • Journal Title: Cancer Res 68 Pages: 1074-82
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinical significance of the reduced expression of G protein gamma7 (GNG7) in oesophageal cancer (2008)
  • Author(s): Ohta, M., 他
  • Journal Title: Br J Cancer 98 Pages: 410-7
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma (2008)
  • Author(s): Sasaki, A., 他
  • Journal Title: Eur J Surg Oncol 34 Pages: 173-9
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion transcript is not found in gastrointestinal and breast cancers (2008)
  • Author(s): Inoue, H., Fukuyoshi, Y., Kita, Y., Utsunomiya, T., Ishida, T., Mori, M
  • Journal Title: Br J Cancer 98(9) Pages: 1536-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Activin a causes cancer cell aggressiveness in esophageal squamous cell carcinoma cells (2008)
  • Author(s): Yoshinaga, K., Yamashita, K., Mimori, K., Tanaka, F., Inoue, H., Mori, M
  • Journal Title: Ann Surg Oncol 15(1) Pages: 96-103
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis (2008)
  • Author(s): Yokoe, T., Tanaka, F., Mimori, K., Inoue, H., Ohmachi, T., Kusunoki, M., Mori, M
  • Journal Title: Cancer Res 68(4) Pages: 1074-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Prognostic value of tumor-infiltrating.FOXP3+regulatory T cells in patients with hepatocellular carcinoma (2008)
  • Author(s): Sasaki, A., Tanaka, F., Mimori, K., Inoue, H., Kai, S., Shibata, K., Ohta, M., Kitano, S., Mori, M
  • Journal Title: Eur J Surg Oncol 34(2) Pages: 173-9
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical Significance of Loss of Fhll Expression in Human Gastric Cancer (2008)
  • Author(s): Sakashita, K., Mimori, K., Tanaka, F., Kamohara, Y., Inoue, H., Sawada, T., Hirakawa, K., Mori, M
  • Journal Title: Ann Surg Oncol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of the reduced expression of G protein gamma 7(GNG7) in oesophageal cancer (2008)
  • Author(s): Ohta, M., Mimori, K., Fukuyoshi, Y., Kita, Y., Motoyama, K., Yamashita, K., Ishii, H., Inoue, H., Mori, M
  • Journal Title: Br J Cancer 98(2) Pages: 410-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical Significance of BMP7 in Human Colorectal Cancer (2008)
  • Author(s): Motoyama, K., Tanaka, F., Kosaka, Y., Mimori, K., Uetake, H., Inoue, H., Sugihara, K., Mori, M
  • Journal Title: Ann Surg Oncol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family (2008)
  • Author(s): Motoyama, K., Inoue, H., Nakamura, Y., Uetake, H., Sugihara, K., Mori, M
  • Journal Title: Clin Cancer Res 14(8) Pages: 2334-40
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell carcinoma (2008)
  • Author(s): Kita, Y., Mimori, K., Tanaka, F., Matsumoto, T., Haraguchi, N., Ishikawa, K., Matsuzaki, S., Fukuyoshi, Y., Inoue, H., Natsugoe, S, Aikou, T., Mori, M
  • Journal Title: Eur J Burg Oncol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biological and genetic characteristics of tumor-initiating cells in colon cancer (2008)
  • Author(s): Ieta, K., Tanaka, F., Haraguchi, N., Kita, Y., Sakashita, H., Mimori, K., Matsumoto, T., Inoue, H., Kuwano, H., Mori, M
  • Journal Title: Ann Surg Oncol 15(2) Pages: 638-48
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical Significance of BMP7 in Human Colorectal Cancer (2008)
  • Author(s): Motoyama, K, 他
  • Journal Title: Ann Surg Oncol
  • Peer Reviewed
• [Journal Article] Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis (2008)
  • Author(s): Yokoe, T., 他
  • Journal Title: Cancer Res 68 Pages: 1074-82
  • Peer Reviewed
• [Journal Article] Clinical significance of the reduced expression of G protein gamma7(GNG7) in oesophageal cancer (2008)
  • Author(s): Ohta, M.
  • Journal Title: Br J Cancer 98 Pages: 410-7
  • Peer Reviewed
• [Journal Article] Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients withhepatocellular carcinoma (2008)
  • Author(s): Sasaki, A., 他
  • Journal Title: Eur J Surg Oncol 34 Pages: 173-9
  • Peer Reviewed
• [Journal Article] Biological and genetic characteristics of tumor-initiating cells incolon cancer (2007)
  • Author(s): leta, K., 他
  • Journal Title: Ann Surg Oncol 68 Pages: 638-48
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease (2007)
  • Author(s): Utsunomiya, T., 他
  • Journal Title: World J Gastroenterol 13 Pages: 383-90
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Opa Interacting Protein 5 (O1P5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer (2007)
  • Author(s): Nakamura, Y., 他
  • Journal Title: Eur J Surg Oncol 33 Pages: 44-8
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer (2007)
  • Author(s): Nakamura, Y., 他
  • Journal Title: Br J Cancer 97 Pages: 543-49
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinical significance of the loss of MATS1 mRNA expression incolorectal cancer (2007)
  • Author(s): Kosaka, Y., 他
  • Journal Title: Int J Oncol 31 Pages: 338-8
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Tripartite motif-containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer (2007)
  • Author(s): Kosaka, Y., 他
  • Journal Title: Ann Surg Oncol 14 Pages: 1543-98
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Identification of overexpressed genes in hepatocellular carcinoma,with special reference to ubiquitin-conjugating enzyme E2C gene expression (2007)
  • Author(s): leta, K., 他
  • Journal Title: Int J Cancer 121 Pages: 33-38
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] BAC clones related to prognosis in patients with esophagealsquamous carcinoma: an array comparative genomic hybridization study (2007)
  • Author(s): Hirasaki, S., 他
  • Journal Title: Oncologist 12 Pages: 406-17
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Clinical significance of growth differentiation factor 11 in colorectal cancer (2007)
  • Author(s): Yokoe, T., Ohmachi, T., Inoue, H., Mimori, K., Tanaka, F., Kusunoki, M., Mori, M
  • Journal Title: Int J Oncol 31(5) Pages: 1097-101
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease (2007)
  • Author(s): Utsunomiya, T., Okamoto, M., Wakiyama, S., Hashimoto, M., Fukuzawa, K., Ezaki, T., Aishima, S.,Yoshikawa, Y., Hanai, T., Inoue, H., Barnard, G.F., Mori, M
  • Journal Title: World J Gastroenterol 13(3) Pages: 383-90
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] TIMP-3 and Phosphatidylinositol 3-kinase Genes Were Found to Be Related to the Progression of Colon Cancer in a Comparison of Pneumoperitoneum and Laparotomy in a Murine Model (2007)
  • Author(s): Tanaka, F., Sonoda, H., Okamoto, M., Mimori, K., Utsunomiya, T., Inoue, H., Hanai, T., Mori, M
  • Journal Title: Surgery Today 37(3) Pages: 220-5
  • NAID: 10018873190
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] BAC clones related to prognosis in patients with esophageal squamous carcinoma : an array comparative genomic hybridization study (2007)
  • Author(s): Hirasaki, S., Noguchi, T., Mimori, K., Onuki, J., Morita, K., Inoue, H., Sugi Mori, M., Hirano, T
  • Journal Title: Oncologist 12(4) Pages: 406-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Biological and genetic characteristics of tumor-initiating cells in colon cancer (2007)
  • Author(s): leta, K., 他
  • Journal Title: Ann Surg Oncol 68 Pages: 638-48
  • Peer Reviewed
• [Journal Article] A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease (2007)
  • Author(s): Utsunomiya, T., 他
  • Journal Title: Worid J Gastroenterol 13 Pages: 383-90
  • Peer Reviewed
• [Journal Article] Opa Interacting Protein5(OIP5) Is aNovel Cancer-testis Specific Gene in Gastric Cancer (2007)
  • Author(s): Nakamura, Y., 他
  • Journal Title: Eur J Surg Oncol 33 Pages: 44-8
  • Peer Reviewed
• [Journal Article] Clinicopathological and biological significance of mitoti ccentromere-associated kinesin overexpression in human gastric cancer (2007)
  • Author(s): Nakamura, Y., 他
  • Journal Title: Br J Cancer 97 Pages: 543-49
  • Peer Reviewed
• [Journal Article] Clinical significance of the loss of MATS1 mRNA expression in colorectal cancer (2007)
  • Author(s): Kosaka, Y., 他
  • Journal Title: Int J Oncol 31 Pages: 338-8
  • Peer Reviewed
• [Journal Article] Tripartite motif-containing 29 (TRIM29) is a novel malker for lymphnode metastasis in gastric cancer (2007)
  • Author(s): Kosaka, Y., 他
  • Journal Title: Ann Surg Oncol 14 Pages: 2543-98
  • Peer Reviewed
• [Journal Article] BAC clones related to prognosis in patients with esophageal squamous carcinoma: an array comparative genomic hybridization study (2007)
  • Author(s): Hirasaki, S., 他
  • Journal Title: Oncologist 12 Pages: 406-17
  • Peer Reviewed
• [Journal Article] Identification of EGFR mutations in esophageal cancer (2006)
  • Author(s): Sudo, T., 他
  • Journal Title: Eur J Surg Oncol 33 Pages: 44-8
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Significance of skp2 expression in primary breast cancer (2006)
  • Author(s): Sonoda, H., 他
  • Journal Title: Clin Cancer Res 12 Pages: 1215-20
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of EGFR mutations in esophageal cancer (2006)
  • Author(s): Sudo, T.他
  • Journal Title: Eur J Surg Oncol 33 Pages: 44-8
• [Journal Article] Significance of skp2 expression in primary breast cancer (2006)
  • Author(s): Sonoda, H.他
  • Journal Title: Clin Cancer Res 12 Pages: 1215-20
• [Journal Article] soecific gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients (2006)
  • Author(s): Okamato, M.他
  • Journal Title: Ann Surg Oncol 13 Pages: 947-954
• [Journal Article] Expression of the TRAG-3 gene in human esophageal cancer : The frequent synchronous expression of MAGE-3 gene (2006)
  • Author(s): Ohta, M.他
  • Journal Title: Oncol Rep 15 Pages: 1529-32
• [Journal Article] Clinical significance of TROP2 expression in colorectal cancer (2006)
  • Author(s): Ohmachi, T.他
  • Journal Title: Clin Cancer Res 12 Pages: 3057-63
• [Journal Article] FHIT is up-regulated by inflammatory stimuli and inhibits prostaglandin E2-mediated cancer progression (2006)
  • Author(s): Mimori, K.他
  • Journal Title: Cancer Res 66 Pages: 2683-90
• [Presentation] 大腸癌の発生および進展に関わる因子の解析:遺伝子多型とアレイ発現解析 (2007)
  • Author(s): 井上 裕
  • Organizer: 日本外科学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-04-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Analysis on the multivariate factors involving the development and advancement of colorectal cancer (2007)
  • Author(s): H., Inoue, et. al.
  • Organizer: 107 Annual Congress of Japan Surgical society
  • Place of Presentation: Oska
  • Year and Date: 2007-04-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 癌ワクチン療法の基礎と臨床 (2007)
  • Author(s): 井上 裕
  • Organizer: 臨床腫瘍学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-03-21
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 消化器癌における遺伝子解析の現状と展望 (2007)
  • Author(s): 井上 裕
  • Organizer: 札幌消化器外科セミナー
  • Place of Presentation: 札幌
  • Year and Date: 2007-02-23
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 大腸癌の発生および進展に関わる因子の解析:遺伝子多型とアレイ発現解析 (2007)
  • Author(s): 井上 裕
  • Organizer: 日本消化管学会
  • Place of Presentation: 東京
  • Year and Date: 2007-02-01
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Genetic polymorphism and gene expression of colorectal cancer : Microarray analysis (2007)
  • Author(s): H., Inoue, et. al.
  • Organizer: The 3rd Annual Meeting of The Japanese Gastroenterological Association
  • Place of Presentation: Tokyo
  • Year and Date: 2007-02-01
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.mib-beppu.kyushu-u.ac.jp/MIB_res/Surgery/
• [Remarks]
  • URL: http://www.mib-beppu.kyushu-u.ac.jp/MIB_res/Surgery/