Potential role of monomeric laminin-gamma 2 as a novel biomarker for hepatocellular carcinoma.

• Project/Area Number: 15K08655
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Yasuda Hiroshi 聖マリアンナ医科大学, 医学部, 教授 (80262129)
• Co-Investigator(Kenkyū-buntansha): 山本 博幸 聖マリアンナ医科大学, 医学部, 准教授 (40332910)
• Research Collaborator: Koshikawa Naohiko
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ラミニンγ２短鎖 / 肝細胞癌 / バイオマーカー / PIVKA-2 / AFP / サーベイランス / ラミニンγ2 / Ln-γ2 / 腫瘍マーカー

Outline of Final Research Achievements

Laminin (Ln)-332 consists of α3, β3, and γ2 chains, which mediate epithelial cell adhesion to the basement membrane. Ln-γ2 is frequently expressed as a monomer in the invasion front of several types of malignant tissues without simultaneous expression of Ln-α3 and/or Ln-β3 chains. Moreover, monomeric Ln-γ2 ( Ln-γ2m) induces tumor cell proliferation and migration in vitro. These unique biological activities indicate that Ln-γ2m could be a candidate biomarker for early cancer surveillance. We have developed monoclonal antibodies to specifically detect Ln-γ2m, and devised a highly sensitive method to measure serum Ln-γ2m levels using a fully automated CLIA. We evaluated its diagnostic value in sera from patients with several digestive cancers, including HCC, and found serum Ln-γ2m to be a clinically available biomarker for HCC surveillance. The combination of Ln-γ2m and PIVKA-2 may be more sensitive for clinical diagnosis of HCC than any currently used combination.

Academic Significance and Societal Importance of the Research Achievements

５大癌の一つである肝癌は、今後ウイルス性肝炎を背景とするものは減少し、サーベイランスが困難な生活習慣病を背景とする非B非C型が増加すると予測される。難治癌である膵癌の罹患率は特に高齢者で増加しており、2013年の死亡数はほぼ肝癌と同数の3万人である。東アジアではウイルス肝炎罹患率が高く、欧米では非アルコール性脂肪肝に伴う肝細胞癌が増加している。肝癌・膵癌の制圧は世界的に重要な課題である。癌の新たなスクリーニング法の確立が急務である。

Research Products

• [Journal Article] Unique Biological Activity and Potential Role of Monomeric Laminin-γ2 as a Novel Biomarker for Hepatocellular Carcinoma: A Review (2019)
  • Author(s): Yasuda Hiroshi、Nakagawa Masatoshi、Kiyokawa Hirofumi、Yoshida Eisaku、Yoshimura Toru、Koshikawa Naohiko、Itoh Fumio、Seiki Motoharu
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 1 Pages: 226-226
  • DOI: 10.3390/ijms20010226
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy of ledipasvir/sofosbuvir with or without ribavirin for 12 weeks in genotype 1b HCV patients previously treated with a nonstructural protein 5A inhibitor-containing regimen (2018)
  • Author(s): Ikeda Hiroki、Watanabe Tsunamasa、Shimizu Hirohito、Hiraishi Tetsuya、Kaneko Rena、Baba Toshiyuki、Takahashi Hideaki、Matsunaga Kotaro、Matsumoto Nobuyuki、Yasuda Hiroshi、Okuse Chiaki、Iwabuchi Shogo、Suzuki Michihiro、Itoh Fumio
  • Journal Title: Hepatology Research Volume: 48 Issue: 10 Pages: 802-809
  • DOI: 10.1111/hepr.13074
  • Open Access
• [Journal Article] Serum monomeric laminin-γ2 as a novel biomarker for hepatocellular carcinoma. (2017)
  • Author(s): Kiyokawa H, Yasuda H, Oikawa R, Okuse C, Matsumoto N, Ikeda H, Watanabe T, Yamamoto H, Itoh F, Otsubo T, Yoshimura T, Yoshida E, Nakagawa M, Koshikawa N, Seiki M.
  • Journal Title: Cancer Science Volume: 108 Issue: 7 Pages: 1432-1439
  • DOI: 10.1111/cas.13261
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of resistance-associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir. (2017)
  • Author(s): Ikeda H, Watanabe T, Okuse C, Matsumoto N, Ishii T, Yamada N, Shigefuku R, Hattori N, Matsunaga K, Nakano H, Hiraishi T, Kobayashi M, Yasuda K, Yamamoto H, Yasuda H, Kurosaki M, Izumi N, Yotsuyanagi H, Suzuki M, Itoh F.
  • Journal Title: J Medical Virology Volume: 89 Issue: 1 Pages: 99-105
  • DOI: 10.1002/jmv.24608
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a FGFR3-TACC3 fusion in esophageal cancer. (2017)
  • Author(s): Mizukami T, Sakai K, Naruki S, Taniyama T, Horie Y, Izawa N, Tsuda T, Fujino T, Boku N, Yasuda H, Fukunaga T, Nakajima TE, Nishio K.
  • Journal Title: Annals of Oncology Volume: 28 Issue: 2 Pages: 437-438
  • DOI: 10.1093/annonc/mdw550
  • Peer Reviewed / Open Access
• [Journal Article] Successful endoscopic fragmentation of large hardened fecaloma using jumbo forceps. (2017)
  • Author(s): Matsuo Y, Yasuda H, Nakano H, Hattori M, Ozawa M, Sato Y, Ikeda Y, Ozawa SI, Yamashita M, Yamamoto H, Itoh F.
  • Journal Title: World J Gastrointest Endosc. Volume: 9 Issue: 2 Pages: 91-94
  • DOI: 10.4253/wjge.v9.i2.91
  • Peer Reviewed / Open Access
• [Journal Article] Twelve-year natural history of a gastric adenocarcinoma of fundic gland type. (2016)
  • Author(s): Sato Y, Fujino T, Kasagawa A, Morita R, Ozawa SI, Matsuo Y, Maehata T, Yasuda H, Takagi M, Itoh F.
  • Journal Title: Clin J Gastroenterol Volume: 9 Issue: 6 Pages: 345-351
  • DOI: 10.1007/s12328-016-0680-5
  • Peer Reviewed / Open Access
• [Journal Article] Can the Abbott RealTime hepatitis C virus assay be used to predict therapeutic outcomes in hepatitis C virus-infected patients undergoing triple therapy? (2016)
  • Author(s): Ikeda H, Okuse C, Watanabe T, Matsumoto N, Matsunaga K, Shigefuku R, Hattori N, Hiraishi T, Fukuda Y, Noguchi Y, Ishii T, Shima J, Nakahara K, Yamamoto H, Yasuda H, Yotsuyanagi H, Koike K, Itoh F, Suzuki M.
  • Journal Title: Turk J Gastroenterol. Volume: 27 Issue: 2 Pages: 165-172
  • DOI: 10.5152/tjg.2016.150300
  • Peer Reviewed / Open Access
• [Journal Article] Urgent Computed Tomography for Determining the Optimal Timing of Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding (2015)
  • Author(s): Nakatsu S, Yasuda H, Maehata T, Nomoto M, Ohinata N, Hosoya K, Ishigooka E, Ozawa S, Ikeda Y, Sato Y, Suzuki M, Kiyokawa H, Yamamoto H, Itoh F.
  • Journal Title: Internal Medicine Volume: 54 Issue: 6 Pages: 553-558
  • DOI: 10.2169/internalmedicine.54.2829
  • NAID: 130004903081
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. (2015)
  • Author(s): Yasuda H, Matsuo Y, Sato Y, Ozawa S, Ishigooka S, Yamashita M, Yamamoto H, Itoh F.
  • Journal Title: World J Critical Care Medicine Volume: 4 Issue: 1 Pages: 40-47
  • DOI: 10.5492/wjccm.v4.i1.40
  • Peer Reviewed / Open Access
• [Journal Article] Hemostasis Achieved Endoscopically for Diverticular Bleeding from the Horizontal Portion of the Duodenum. (2015)
  • Author(s): Matsuo Y, Yasuda H, Suzuki M, Ishigooka S, Ozawa S, Yamashita M, Yamamoto H, Itoh F.
  • Journal Title: Clin Med Insights Gastroenterol Volume: 8 Pages: 61-64
  • DOI: 10.4137/cgast.s32421
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Role of COX-2 gene promoter methylation and Helicobacter pylori infection in gastric ulcer healing. (2018)
  • Author(s): Yasuda, Hiroshi; Watanabe, Yoshiyuki; Itoh, Fumio.
  • Organizer: 米国消化器関連週間
  • Int'l Joint Research
• [Presentation] ：肝細胞癌に対するTACE後治療効果判定における血清ラミニンγ2単鎖の有用性 (2018)
  • Author(s): 近江亮介，清川博史，松本伸行，奥瀬千晃，中川将利，吉田栄作，吉村 徹，越川直彦，安田 宏，伊東文生
  • Organizer: 日本消化器関連週間
• [Presentation] Serum monomeric laminin-γ2 as a novel biomarker for hepatocellular carcinoma. (2017)
  • Author(s): Kiyokawa H, Yasuda H, Okuse C, Matsumoto N, Yoshimura T, Yoshida R, Nakagawa M. Seiki M, Koshikawa N. Itoh F.
  • Organizer: American Gastroenterological Association
  • Int'l Joint Research
• [Presentation] 新たな肝細胞がん診断のバイオマーカーの同定 (2016)
  • Author(s): 越川直彦、安田宏、清川博史、伊東文生、中川将利、吉田栄作、吉村徹、清木元治
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-07
• [Presentation] 肝細胞癌の新規バイオマーカーの開発 (2016)
  • Author(s): 清川博史，安田 宏，中川将利，吉田栄作，吉村 徹，清木元治，越川直彦，清木元治、伊東文生.
  • Organizer: 第36回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-05
• [Presentation] 肝細胞癌の新規腫瘍マーカーの探索 (2016)
  • Author(s): 清川博史、越川直彦、安田宏、清木元治、伊東文生.
  • Organizer: 第67回日本電気泳動学会総会
  • Place of Presentation: 釧路市観光交流センター（北海道釧路市）
  • Year and Date: 2016-08-26
• [Presentation] 新規肝癌腫瘍マーカーとしての血清ラミニンγ2単鎖の有用性 (2016)
  • Author(s): 清川博史，安田 宏，松本伸行，石井俊哉，奥瀬千晃，山本博幸，中川将利，吉田栄作，吉村 徹，清木元治，越川直彦，伊東文生.
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張（千葉県千葉市）
  • Year and Date: 2016-05-20
• [Presentation] 新規肝癌腫瘍マーカーとしての細胞外マトリックス関連分子の有用性 (2015)
  • Author(s): 清川博史，安田宏，松本伸行，奥瀬千晃，石井俊哉，山本博幸，伊東文生，吉田栄作，吉村徹，越川直彦，清木元治
  • Organizer: 第21回日本消化器関連学会週間JDDW 2015
  • Place of Presentation: 東京・グランドプリンスホテル新高輪
  • Year and Date: 2015-10-08
• [Book] 人体の正常構造と機能 改訂第3版、Ⅳ肝胆膵 (2017)
  • Author(s): 安田宏、眞嶋浩聡、大野秀樹
  • Total Pages: 879
  • Publisher: 日本医事新報社
  • ISBN: 9784784931804
• [Book] 人体の正常構造と機能 改訂第3版、Ⅳ肝胆膵 (2017)
  • Author(s): 安田宏
  • Total Pages: 72
  • Publisher: 日本医事新報社