Utility of cell-free TERRA packaged in extracellular vesicles as circulating cancer biomarker.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15656
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tokyo Medical University
• Principal Investigator: Kobayashi Chiaki 東京医科大学, 医学部, 助手 (20747828)
• Research Collaborator: OHYASHIKI junko
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: テロメアRNA / エクソソーム / 骨髄異形成症候群 / リキッドバイオプシー

Outline of Final Research Achievements

Despite the fact that telomere dysfunction is frequently seen in tumor, little is known about telomere repeat-containing RNA (TERRA) that regulates telomere dynamics. Emerging evidences suggest that extracellular vesicles (EVs) in cell-free (cf) fraction act as a mediator of cell-cell interaction in human cancer. The EVs contain long non-coding RNA, including telomere repeat-containing RNA (TERRA). To determine whether cf-TERRA could be a molecular marker for treating myelodysplastic syndrome (MDS) patients, we analyzed both TERRA and cf-TERRA in this study. We evaluated the TERRA localization in BM samples obtained from MDS patients. The TERRA foci were significantly increased in post-MDS AML compared with untreated MDS.
Notably, the cf-TERRA in EVs could reflect TERRA expression levels in BM cells. Our results suggest that increased TERRA expression might be Instead of BM cells, cf-TERRA could be a putative molecular marker for treating MDS patients.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は（1）体液診断の一環として、（2） エクソソームを試料とし、（3）テロメア制御分子であるTERRAをバイオマーカーとして臨床応用するための検出系を構築することである。本研究の成果が臨床応用されれば、テロメア動態の非侵襲的モニタリングが可能となる。また、固形腫瘍のみならず、造血器腫瘍においても、末梢血液中に腫瘍細胞が出現していない病態、たとえば骨髄浸潤のない悪性リンパ腫や多発性骨髄腫、そして造血幹細胞移植後などにおいて、がん個別化医療の実現にむけて臨床的意義は大きい。以上、従来のCTC解析と異なり、本手法は造血器腫瘍を含めたがん全体の体液診断への新たなアプローチとなりえる。