Development of method detecting early stage non-viral liver cancer using innate immune factors as new biomarker.

• Project/Area Number: 17K09159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Yamaguchi University
• Principal Investigator: Tanabe Tsuyoshi 山口大学, 大学院医学系研究科, 教授 (80260678)
• Co-Investigator(Kenkyū-buntansha): 山口 奈津 山口大学, 大学院医学系研究科, 助教 (40450671) ; 高橋 秀和 山口大学, 大学院医学系研究科, 講師 (90450402) ; 中上 裕有樹 下関市立大学, 経済学研究科, 准教授 (30843304)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 非ウイルス性肝がん / microRNA / SNP / バイオマーカー / エクソソーム / ctDNA / 早期診断 / 非B非C肝がん / マイクロRNA

Outline of Final Research Achievements

Non-viral hepatocellular carcinoma, which has been rapidly increasing in recent years, is often discovered at an advanced stage because high-risk groups cannot be identified and early diagnosis is difficult. Therefore, establishment of a screening method for early diagnosis is desired. In this study, we investigated the relationship between the development of non-viral hepatocellular carcinoma and the gene polymorphisms of innate immune factors and the expression levels of circulating microRNAs. As a result, changes in the expression levels of miR-150 and miR-210 among circulating microRNAs were associated with statistical significance. These results should be validated in larger populations.

Academic Significance and Societal Importance of the Research Achievements

本研究は、非ウイルス性肝がん症例および糖尿病症例より得られた血液検体を用いて自然免疫因子の遺伝子多型および血中microRNAの発現解析を行い、非ウイルス性肝がん症例で発現量が有意に変化するmicroRNAを明らかにした。今後、より大きな集団で検証することにより、本研究成果を早期診断のためのバイオマーカーとして応用することを目指す。ウイルス性肝がんに比較して、非ウイルス性肝がんのバイオマーカーに関する知見はいまだ乏しいことから、本研究は学術的・社会的に意義があるものと考える。

Research Products

• [Journal Article] Association of Plasma Branched-Chain and Aromatic Amino Acids with Reduction in Kidney Function Evaluated in Apparently Healthy Adults (2021)
  • Author(s): Mahbub MH、Yamaguchi Natsu、Nakagami Yuki、Hase Ryosuke、Takahashi Hidekazu、Ishimaru Yasutaka、Watanabe Rie、Saito Hiroyuki、Shimokawa Junki、Yamamoto Hiroshi、Kikuchi Shinya、Tanabe Tsuyoshi
  • Journal Title: Journal of Clinical Medicine Volume: 10 Issue: 22 Pages: 5234-5234
  • DOI: 10.3390/jcm10225234
  • Peer Reviewed
• [Journal Article] Analysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation (2021)
  • Author(s): Takahashi Hidekazu、Okayama Naoko、Yamaguchi Natsu、Nomura Moe、Miyahara Yuta、Mahbub MH、Hase Ryosuke、Morishima Yasuo、Suehiro Yutaka、Yamasaki Takahiro、Tamada Koji、Takahashi Satoshi、Tojo Arinobu、Tanabe Tsuyoshi
  • Journal Title: Cancers Volume: 13 Issue: 11 Pages: 2752-2752
  • DOI: 10.3390/cancers13112752
  • Peer Reviewed / Open Access
• [Journal Article] A novel mutation in early‐onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes (2021)
  • Author(s): Okazaki Fumiko、Wakiguchi Hiroyuki、Korenaga Yuno、Nakamura Tamaki、Yasudo Hiroki、Uchi Shohei、Yanai Ryoji、Asano Nobuyuki、Hoshii Yoshinobu、Tanabe Tsuyoshi、Izawa Kazushi、Honda Yoshitaka、Nishikomori Ryuta、Uchida Keisuke、Eishi Yoshinobu、Ohga Shouichi、Hasegawa Shunji
  • Journal Title: Pediatric Rheumatology Volume: 19 Issue: 1 Pages: 18-18
  • DOI: 10.1186/s12969-021-00505-5
  • Peer Reviewed / Open Access
• [Journal Article] Acute Effects of Whole-Body Vibration on Peripheral Blood Flow, Vibrotactile Perception and Balance in Older Adults (2020)
  • Author(s): Mahbub M. H.、Hase Ryosuke、Yamaguchi Natsu、Hiroshige Keiichi、Harada Noriaki、Bhuiyan A. N. M. Nurul Haque、Tanabe Tsuyoshi
  • Journal Title: International Journal of Environmental Research and Public Health Volume: 17 Issue: 3 Pages: 1069-1069
  • DOI: 10.3390/ijerph17031069
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasma Branched-Chain and Aromatic Amino Acids in Relation to Hypertension (2020)
  • Author(s): Mahbub M. H.、Yamaguchi Natsu、Hase Ryosuke、Takahashi Hidekazu、Ishimaru Yasutaka、Watanabe Rie、Saito Hiroyuki、Shimokawa Junki、Yamamoto Hiroshi、Kikuchi Shinya、Tanabe Tsuyoshi
  • Journal Title: Nutrients Volume: 12 Issue: 12 Pages: 3791-3791
  • DOI: 10.3390/nu12123791
  • Peer Reviewed / Open Access
• [Journal Article] The different roles of innate immune receptors in inflammation and carcinogenesis between races (2017)
  • Author(s): Natsu Yamaguchi, Yoshimi Suzuki, M. H. Mahbub, Hidekazu Takahashi, Ryosuke Hase, Yasutaka Ishimaru, Hiroshi Sunagawa, Rie Watanabe, Yoshinobu Eishi, Tsuyoshi Tanabe
  • Journal Title: Environ Health Prev Med Volume: 22 Issue: 1 Pages: 70-70
  • DOI: 10.1186/s12199-017-0678-8
  • NAID: 210000130245
  • Peer Reviewed / Open Access
• [Journal Article] Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus, dyslipidemia, hypertension and metabolic syndrome (2017)
  • Author(s): Mahbub MH, Yamaguchi N, Takahashi H, Hase R, Ishimaru Y, Sunagawa H, Amano H, Kobayashi-Miura M, Kanda H, Fujita Y, Yamamoto H, Yamamoto M, Kikuchi S, Ikeda A, Kageyama N, Nakamura M, Tanabe T
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-017-17710-6
  • Peer Reviewed / Open Access
• [Journal Article] Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population. (2017)
  • Author(s): Yamaguchi N, Mahbub MH, Takahashi H, Hase R, Ishimaru Y, Sunagawa H, Amano H, Kobayashi-Miura M, Kanda H, Fujita Y, Yamamoto H, Yamamoto M, Kikuchi S, Ikeda A, Takasu M, Kageyama N, Nakamura M, Tanabe T.
  • Journal Title: Environ Health Prev Med. Volume: 22 Issue: 1 Pages: 22-35
  • DOI: 10.1186/s12199-017-0642-7
  • Peer Reviewed / Open Access
• [Journal Article] Associations of interactions between NLRP3 SNPs and HLA mismatch with acute and extensive chronic graft-versus-host diseases (2017)
  • Author(s): Hidekazu Takahashi, Naoko Okayama, Natsu Yamaguchi, Yuta Miyahara, Yasuo Morishima, Yutaka Suehiro, Takahiro Yamasaki, Koji Tamada, Satoshi Takahashi, Arinobu Tojo, Shigetaka Asano & Tsuyoshi Tanabe
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 13097-13097
  • DOI: 10.1038/s41598-017-13506-w
  • Peer Reviewed / Open Access