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Title :Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL
Authors :Guerrero, Carmina Louise Hugo
Issue Date :20-Mar-2020
Abstract :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.
URL :https://doi.org/10.1182/bloodadvances.2019001429
Type Local :学位論文
Publisher :University of the Ryukyus
URI :http://hdl.handle.net/20.500.12000/47433
Grant id :18001保健研第23号
Date of granted :2020-09-18
Degree name :博士(保健学)
Grantor :琉球大学
Citation :Blood Advances Vol.4 no.6 p.1062 -1071
Appears in Collections:Doctoral Dissertation (Graduate School of Health Sciences)

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