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Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL
http://hdl.handle.net/20.500.12000/47433
http://hdl.handle.net/20.500.12000/474336a462a4e-e2fa-4f58-88e5-17e69d6ea0a2
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hokenken23visual abstract.pdf
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hokenken23text.pdf
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hokenken23review.pdf
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hokenken23abstract.pdf
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Item type | デフォルトアイテムタイプ(フル)(1) | |||||||
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公開日 | 2020-12-08 | |||||||
タイトル | ||||||||
タイトル | Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL | |||||||
言語 | en | |||||||
作成者 |
Guerrero, Carmina Louise Hugo
× Guerrero, Carmina Louise Hugo
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アクセス権 | ||||||||
アクセス権 | open access | |||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
内容記述 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | AdultT-cell leukemia/lymphoma (ATL) is ahuman T-cell leukemia virus type 1 (HTLV-1)–associated T-cell malignancy with generally poor prognosis. Although only ;5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n 5 40; ATL, n 5 40; remission, n 5 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor receptor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch’s t test P , .00001), high discrimination capacity (area under the curve .0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n530; ATL, n568; remission, n54) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL. | |||||||
内容記述 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | 学位論文 | |||||||
出版者 | ||||||||
言語 | en | |||||||
出版者 | University of the Ryukyus | |||||||
言語 | ||||||||
言語 | eng | |||||||
資源タイプ | ||||||||
資源タイプ | doctoral thesis | |||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
出版タイプ | ||||||||
出版タイプ | VoR | |||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
識別子 | ||||||||
識別子 | http://hdl.handle.net/20.500.12000/47433 | |||||||
識別子タイプ | HDL | |||||||
関連情報 | ||||||||
識別子タイプ | DOI | |||||||
関連識別子 | https://doi.org/10.1182/bloodadvances.2019001429 | |||||||
関連情報 | ||||||||
識別子タイプ | DOI | |||||||
関連識別子 | https://doi.org/10.1182/bloodadvances.2019001429 | |||||||
収録物名 | ||||||||
言語 | en | |||||||
収録物名 | Blood Advances | |||||||
書誌情報 |
巻 4, 号 6, p. 1062-1071, 発行日 2020-03-20 |
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学位授与番号 | ||||||||
学位授与番号 | 甲第23号 | |||||||
学位名 | ||||||||
学位名 | 博士(保健学) | |||||||
言語 | ja | |||||||
学位授与年月日 | ||||||||
学位授与年月日 | 2020-09-18 | |||||||
学位授与機関 | ||||||||
学位授与機関識別子 | 18001 | |||||||
学位授与機関識別子Scheme | kakenhi | |||||||
学位授与機関名 | 琉球大学 | |||||||
言語 | ja |