Identification of novel methylation markers in HPV-associated oropharyngeal cancer for precision medicine
| Project/Area Number |
17K16904
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
Imai Atsushi 浜松医科大学, 医学部附属病院, 助教 (30794309)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | HPV関連癌 / リキッドバイオプシー / 中咽頭癌 / メチル化 / cell free DNA / 循環腫瘍DNA / 頭頸部癌 / 個別化医療 / 腫瘍循環細胞 / メチル化解析 |
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| Outline of Final Research Achievements |
Genome-wide discovery using RNA sequencing and reduced representation bisulfite sequencing yielded 21 candidates for methylation-targeted genes. A verification study using Q-MSP identified 10 genes that showed an increase recurrence in methylation groups with oropharyngeal cancer (OPC). Further study on ctDNA in HPV-associated OPC showed that three genes (CALML5, DNAJC5G, and LY6D) had a high predictive ability as emerging biomarkers for a validation set, each capable of discriminating between the plasma of the patients from healthy individuals. Among pre-treatment ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 8/8 (100%), 7/8 (87.5%), and 7/8 (87.5%) samples, respectively. Methylated CALML5, DNAJC5G, and LY6D were found in 2/8 (25.0%), 0/8 (0%), and 1/8 (12.5%) of the final samples in the series, respectively. Here, we present the relationship between the methylation status of three genes and cancer recurrence for risk classification of HPV-associated OPC cases.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究は、リキッドバイオプシーによるHPV関連中咽頭癌の腫瘍状態を見極められるマーカーを探索することが目的であった。3種類の遺伝子のDNAメチル化を調べることによって治療後の腫瘍の状態、再発による腫瘍の増大を検知できる手法を開発することができた。従来、CT、MRI、PET-CTによる画像評価が治療に行われていたが、患者への負担が少ない採血から得られたctDNAによって、腫瘍の状態を評価することができ今後の臨床に応用されていくことが期待される。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: A site-specific analysis2018
Author(s)
Misawa K, Mima M, Imai A, Mochizuki D, Misawa Y, Endo S, Ishikawa R, Kanazawa T and Mineta H
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Journal Title
Clinical Epigenetics
Volume: 10
Issue: 1
Pages: 52-52
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genes encoding neuropeptide receptors are epigenetic markers in patients with head and neck cancer: a site-specific analysis2017
Author(s)
Misawa K, Imai A, Mochizuki D, Misawa Y, Endo S, Hosokawa S, Ishikawa R, Mima M, Shinmura K, Kanazawa T, Mineta H
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Journal Title
Oncotarget
Volume: 8(44)
Issue: 44
Pages: 76318-76328
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.2017
Author(s)
Misawa Y, Misawa K, Kawasaki H, Imai A, Mochizuki D, Ishikawa R, Endo S, Mima M, Kanazawa T, Iwashita T, Mineta H.
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Journal Title
Tumour Biol.
Volume: 39
Issue: 7
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access
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