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Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma.

ABSTRACT: BACKGROUND: We undertook a study to evaluate the clinical relevance of miR-92a in plasma obtained from non-Hodgkin's lymphoma (NHL) patients, because the miR-17-92 polycistronic miRNA cluster plays a crucial role in lymphomagenesis and affects neo-angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Plasma miR-92a values in NHL were extremely low (<5%), compared with healthy subjects (P<.0001), irrespective of lymphoma sub-type. The very low plasma level of miR-92a increased in the complete response (CR) phase but did not reach the normal range, and the plasma level was lower again in the relapse phase. Patients in CR or CR unconfirmed with a plasma miR-92a level of less than the cut-off level showed a significantly high relapse rate compared with patients with normalized plasma miR-92a level. CONCLUSIONS/SIGNIFICANCE: The current results therefore indicate that the plasma miR-92a value could be a novel biomarker not only for diagnosis but also for monitoring lymphoma patients after chemotherapy.

SUBMITTER: Ohyashiki K

PROVIDER: S-EPMC3044711 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma.

Ohyashiki Kazuma K Umezu Tomohiro T Yoshizawa Sei-Ichiro S Ito Yoshikazu Y Ohyashiki Michiyo M Kawashima Hisashi H Tanaka Masami M Kuroda Masahiko M Ohyashiki Junko H JH

PloS one 20110224 2

<h4>Background</h4>We undertook a study to evaluate the clinical relevance of miR-92a in plasma obtained from non-Hodgkin's lymphoma (NHL) patients, because the miR-17-92 polycistronic miRNA cluster plays a crucial role in lymphomagenesis and affects neo-angiogenesis.<h4>Methodology/principal findings</h4>Plasma miR-92a values in NHL were extremely low (<5%), compared with healthy subjects (P<.0001), irrespective of lymphoma sub-type. The very low plasma level of miR-92a increased in the complet ...[more]

PMID: 21383985

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Project description:BACKGROUND: Plasma microRNA (miRNA) has become a promising biomarker for detecting cancer; however, it remains uncertain whether miRNA expression levels in plasma reflect those in tumor cells. Our aim was to determine the biological relevance of miR-92a, which has been implicated as an oncomiR in both plasma and leukemia cells in patients with acute leukemia and to evaluate whether it could be a novel biomarker for monitoring these patients. RESULTS: We quantified the expression level of miR-92a in both cells and plasma by reverse transcription polymerase chain reaction in 91 patients with acute leukemia. We also determined miR-92a expression levels in peripheral blood mononuclear cells (PBMNC) from normal controls. We compared miR-92a expression in plasma with its expression in leukemia cells. Synthetic anti-miR-92a inhibitor was transfected into Raji and OM9;22 cells, and apoptosis was assessed. For in vivo assessment, 6-week-old female nude mice were injected with U937 cells, and miR-92a expression in plasma and tumors was measured. The level of miR-92a expression in fresh leukemia cells was highly variable compared with PBMNC, but significantly lower compared with CD34-positive cells obtained from healthy volunteers. We also noticed that miR-92a was preferentially expressed in acute lymphoblastic leukemia (ALL) cells in comparison with acute myeloid leukemia (AML) cells. More specifically, cellular miR-92a expression was significantly increased in a subset of ALL cells, and ALL patients with overexpressed miR-92a had poor prognoses. The anti-miR-92a inhibitor-treated Raji and OM9;22 cells revealed an increase of apoptotic cells. Notably, the cell to plasma ratio of miR-92a expression was significantly higher in both AML and ALL cells compared with PBMNC from healthy volunteers. In tumor-bearing mice, the plasma miR-92a level was significantly decreased in accordance with tumor growth, while tumor tissue was strongly positive for miR-92a. CONCLUSIONS: The miR-92a expression in leukemia cells could be a prognostic factor in ALL patients. The inverse correlation of miR-92a expression between cells and plasma and the cell to plasma ratio may be important to understanding the clinical and biological relevance of miR-92a in acute leukemia.

Dataset Information

Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma.

Publications

Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma.

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