Comprehensive analysis of genetic abnormalities in gastrointestinal cancers and the identification of molecular targeted therapy targeting those alterations

• Project/Area Number: 23790800
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: NOSHO Katsuhiko 札幌医科大学, 医学部, 助教 (10597339)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 下部消化管学(小腸、大腸) / 大腸癌 / microRNA / 大腸鋸歯状病変

Research Abstract

The number of elderly colorectal cancer (CRC) patients is expected to increase because of the aging populations in many countries. Previous studies in the U.S. and European countries have shown that the clinical and molecular features of elderly CRC patients were female, right-side colon, BRAF mutation, MLH1 methylation and microsatellite instability (MSI) and that the precursor lesions of those CRCs appeared to be serrated lesions. With regard to Japan, the population is aging much faster than that of any other countries; however, there has been no study on the characteristics of CRCs and serrated lesions in a large population of elderly Japanese patients. We therefore conducted a retrospective large-scale Japanese cohort study and examined the clinicopathological and molecular features of elderly patients.

Research Products

• [Journal Article] PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. (2013)
  • Author(s): Hironobu Shigaki
  • Journal Title: Clinical Cancer Research Volume: in press
  • Peer Reviewed
• [Journal Article] Alterations in the HER2-PI3K-Akt pathway in gastric cancer. (2012)
  • Author(s): Sukawa Y, Yamamoto H, Nosho K, Kunimoto H, Suzuki H, Adachi Y, Nakazawa M, Nobuoka T, Kawayama M, Mikami M, MatunoT, Hasegawa T, Hirata K, Imai K, Shinomura Y.
  • Journal Title: World J Gastroenterol. Volume: 18 Pages: 6577-86
  • Peer Reviewed
• [Journal Article] Expression Profiling of Archival Tumors for Longterm Health Studies. (2012)
  • Author(s): Waldron L, Ogino S, Hoshida Y, Shima K, McCart Reed AE, Simpson PT, Baba Y, Nosho K, Segata N, Vargas AC, Cummings MC, Lakhani SR, Kirkner GJ, Giovannucci E, Quackenbush J, Golub TR, Fuchs CS, Parmigiani G, Huttenhower C.
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 6136-46
  • Peer Reviewed
• [Journal Article] Aspirin use, tumor PIK3CA mutation, and colorectalcancer survival. (2012)
  • Author(s): Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S.
  • Journal Title: N Engl J Med. Volume: 367 Pages: 1596-606
  • Peer Reviewed
• [Journal Article] IGFI receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers. (2012)
  • Author(s): Ohashi H, Adachi Y, Yamamoto H, Taniguchi H, Nosho K, Suzuki H, Arimura Y, Imai K, Carbone DP, Shinomura Y.
  • Journal Title: Cancer Sci Volume: 103 Pages: 252-61
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. (2012)
  • Author(s): Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y.
  • Journal Title: Cancer Res Volume: 72 Pages: 1126-36
  • NAID: 10031131121
  • Peer Reviewed
• [Journal Article] Predictors of lymph node count in colorectal cancer resections: Data from U.S. Nationwide prospective cohort studies. (2012)
  • Author(s): Morikawa T*, Tanaka N*, Kuchiba A*, Nosho K*, Yamauchi M, Hornick JL, Swanson RS, Chan AT, Meyerhardt JA, Huttenhower C, Schrag D, Fuchs CS, Ogino S.
  • Journal Title: Arch Surg Volume: 147 Pages: 715-23
  • Peer Reviewed
• [Journal Article] Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review. (2012)
  • Author(s): Liao X, Morikawa T, Lochhead P, Imamura Y, Kuchiba A, Yamauchi M, Nosho K, Qian ZR, Nishihara R, Meyerhardt JA, Fuchs CS, Ogino S.
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 2257-68
  • Peer Reviewed
• [Journal Article] Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression. (2012)
  • Author(s): Lin JH, Morikawa T, Chan AT, Kuchiba A, Shima K, Nosho K, Kirkner G, Zhang SM, Manson JE, Giovannucci E, Fuchs CS, Ogino S.
  • Journal Title: Cancer Res. Volume: 72 Pages: 3020-8
  • Peer Reviewed
• [Journal Article] The effective molecular targeted therapies for gastroenterological tumors (2012)
  • Author(s): Nosho K, Shinomura Y
  • Journal Title: Medical Science Digest Volume: 38 Pages: 154-7
  • Peer Reviewed
• [Journal Article] Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival (2012)
  • Author(s): Xiaoyun Liao
  • Journal Title: New England Journal of Medicine Volume: 367 Issue: 17 Pages: 1596
  • DOI: 10.1056/nejmoa1207756
  • Peer Reviewed
• [Journal Article] Prognostic role of PIK3CA mutation in colorectal cancer: Cohort study and literature review (2012)
  • Author(s): Xiaoyun Liao
  • Journal Title: Clinical Cancer Research Volume: 18 Issue: 8 Pages: 2257
  • DOI: 10.1158/1078-0432.ccr-11-2410
  • Peer Reviewed
• [Journal Article] Predictors of lymph node count in colorectal cancer resections: Data from U.S. nationwide prospective cohort studies. (2012)
  • Author(s): Morikawa Teppei
  • Journal Title: Archieves of Surgery Volume: 147 Pages: 715-723
  • Peer Reviewed
• [Journal Article] Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer (2012)
  • Author(s): Sukawa Y, Yamamoto H (他11名), Nosho K, Shinomura Y
  • Journal Title: World J Gastroenterol Volume: 18 Issue: 45 Pages: 6577-6586
  • DOI: 10.3748/wjg.v18.i45.6577
  • Peer Reviewed
• [Journal Article] Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. (2012)
  • Author(s): Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, et al.
  • Journal Title: Cancer Res. Volume: 72 Pages: 1126-36
  • NAID: 10031131121
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers. (2012)
  • Author(s): Ohashi H, Adachi Y, Yamamoto H, Taniguchi H, Nosho K, et al.
  • Journal Title: Cancer Sci. Volume: 103 Pages: 252-61
  • Peer Reviewed
• [Journal Article] Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review. (2012)
  • Author(s): Liao X, Morikawa T, Lochhead P, Imamura Y, Kuchiba A, Yamauchi M, Nosho K, et al.
  • Journal Title: Clin Cancer Res. Volume: 18 Pages: 2257-68
  • Peer Reviewed
• [Journal Article] STAT3 Expression, Molecular Features, Inflammation Patterns and Prognosis in a Database of 724 Colorectal Cancers. (2011)
  • Author(s): Morikawa T, Baba Y, Yamauchi M, Kuchiba A, Nosho K, Shima K, Tanaka N, Huttenhower C, Frank DA, Fuchs CS, Ogino S.
  • Journal Title: Clin Cancer Res. Volume: 17 Pages: 1452-62
  • Peer Reviewed
• [Journal Article] MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers. (2011)
  • Author(s): Shima K, Morikawa T, Baba Y, Nosho K, Suzuki M, Yamauchi M, Hayashi M, Giovannucci E, Fuchs CS, Ogino S
  • Journal Title: Cancer Causes Control Volume: 22 Pages: 301-9
  • Peer Reviewed
• [Journal Article] Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. (2011)
  • Author(s): Baba Y*, Nosho K*, Shima K*, Hayashi M, Meyerhardt JA, Chan AT, Giovannucci E, Fuchs CS, Ogino S.
  • Journal Title: Cancer. Volume: 117 Pages: 1399-408
  • Peer Reviewed
• [Journal Article] Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: Cohort study and literature review (2011)
  • Author(s): Shima K*, Nosho K*, Baba Y*, Cantor M, Meyerhardt JA, Giovannucci EL, Fuchs CS, Ogino S.
  • Journal Title: Int J Cancer Volume: 128 Pages: 1080-94
  • Peer Reviewed
• [Journal Article] Association of CTNNB1 (β-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. (2011)
  • Author(s): Morikawa T, Kuchiba A, Yamauchi M, Meyerhardt JA, Shima K, Nosho K, Chan AT, Giovannucci E, Fuchs CS, Ogino S.
  • Journal Title: JAMA Volume: 305 Pages: 1685-94
  • Peer Reviewed
• [Journal Article] Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer. (2011)
  • Author(s): Morikawa T, Kuchiba A, Yamauchi M, Meyerhardt JA, Shima K, Nosho K, et al.
  • Journal Title: JAMA Volume: 305 Pages: 1685-94
  • Peer Reviewed
• [Journal Article] Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers. (2011)
  • Author(s): Baba Y, Nosho K, Shima K, Hayashi M, Meyerhardt JA, et al.
  • Journal Title: Cancer Volume: 117 Pages: 1399-408
  • Peer Reviewed
• [Journal Article] STAT3 expression, molecular features, inflammation patterns, and prognosis in a database of 724 colorectal cancers. (2011)
  • Author(s): Morikawa T, Baba Y, Yamauchi M, Kuchiba A, Nosho K, et al.
  • Journal Title: Clin Cancer Res. Volume: 17 Pages: 1452-62
  • Peer Reviewed
• [Journal Article] MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers. (2011)
  • Author(s): Shima K, Morikawa T, Baba Y, Nosho K, Suzuki M, et al.
  • Journal Title: Cancer Causes Control. Volume: 22 Pages: 301-9
  • Peer Reviewed
• [Presentation] 大腸腫瘍における KRAS、 BRAF、PIK3CA 変異と相関を示す microRNA の同定を目指したアレイシステムによる網羅的 (2013)
  • Author(s): 能正勝彦
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] マルチバイオマーカー解析に基づく切除不能大腸癌の化学療法・分子標的治療の展望 (2013)
  • Author(s): 能正勝彦
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] The relation of LINE methylation level and macroscopic type in colorectal adenoma and pT1 colorectal cancer (2013)
  • Author(s): Katsuhiko Nosho
  • Organizer: Ninth AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Hawaii, USA
• [Presentation] 大腸癌における LINE-1 メチル化レベルと microRNA 発現を標的とした診断・個別化治療への応用 (2013)
  • Author(s): 能正勝彦
  • Organizer: 第9回日本消化管学会総会学術集会
  • Place of Presentation: 東京都
• [Presentation] 大腸腫瘍におけるKRAS、BRAF、PIK3CA変異と相関を示すmicroRNAの同定を目指したアレイシステムによる網羅的検討 (2013)
  • Author(s): 能正 勝彦
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] マルチバイオマーカー解析に基づく切除不能大腸癌の化学療法・分子標的治療の展望 (2013)
  • Author(s): 能正 勝彦
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] 本邦における大腸腺腫・大腸鋸歯状病変と喫煙習慣・BRAF遺伝子変異の検討 (2013)
  • Author(s): 五十嵐 央祥
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 鹿児島県鹿児島市
• [Presentation] The relation of LINE methylation level and macroscopic type in colorectal adenoma and pT1 colorectal cancer (2013)
  • Author(s): Katsuhiko Nosho
  • Organizer: 第9回 日米癌合同会議
  • Place of Presentation: 米国・マウイ
• [Presentation] 大腸癌のグローバル DNA メチル化、microRNA 異常発現の解析とそれらを標的とした新規バイオマーカーの探索と大腸発癌の検討 (2012)
  • Author(s): 能正勝彦
  • Organizer: 第23回日本消化器癌発生学会
  • Place of Presentation: 徳島県鳴門市
• [Presentation] 大腸癌の分子診断学におけるLINE-1 メチル化レベルの重要性と microRNA発現の網羅的解析 (2012)
  • Author(s): 能正勝彦
  • Organizer: JDDW2012
  • Place of Presentation: 兵庫県神戸市
• [Presentation] Comprehensive analysis of the genome-wide DNA methylation and microRNA expression in gastrointestinal cancers and the identification of new biomarkers targeting those alterations (2012)
  • Author(s): 能正勝彦
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道札幌市
• [Presentation] Comprehensive analysis of the genome-wide DNA methylation and microRNA expression in gastrointestinal cancers and the identification of new biomarkers targeting those alterations (2012)
  • Author(s): 能正 勝彦
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: 北海道札幌市
  • Invited
• [Presentation] 新たなphenotypeとしてのLINE-1 extreme hypomethylator phenotype (LEHP) の可能性
  • Author(s): 能正勝彦、五十嵐央祥 、須河恭敬 、山本博幸、足立靖 、荻野周史 、篠村恭久
  • Organizer: 第109回日本内科学会総会
  • Place of Presentation: 京都
• [Presentation] 大規模前向きコホート研究を用いた大腸癌における腫瘍浸潤T細胞と分子生物学的異常・予後との関係
  • Author(s): 能正勝彦、山本博幸、篠村恭久
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] 大腸発癌におけるSerrated polyp pathwayの重要性とfield cancerization
  • Author(s): 能正勝彦、山本博幸、篠村恭久
  • Organizer: 第109回消化器病学会北海道支部例会(招待講演)
  • Place of Presentation: 札幌
• [Presentation] 大腸癌におけるinsulin-like growth factor 2 (IGF2) DMRのmethylation levelの低下と生物学的悪性度との関係
  • Author(s): 能正勝彦、馬場祥史、足立靖、篠村恭久
  • Organizer: 第53回Japan Digestive Disease Week (JDDW)
  • Place of Presentation: 福岡