MicroRNAs in diffuse large B-cell lymphoma

Ni, Huiyun; Tong, Rong; Zou, Lin; Song, Guoqi; Cho, William C.

doi:10.3892/ol.2015.4064

Cited by 17 publications

(11 citation statements)

References 87 publications

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“…Circulating miRNAs are very attractive candidates as non-invasive biomarkers for their high stability in serum/plasma, specificity, sensitivity and predictive power on disease stage and treatment response [ 45 – 48 ]. Moreover, miRNAs may be detected at low quantities, even at picogram concentrations [ 20 ] thus, their expression is likely to be more robust in the determination of cellular origin of multiple cancers [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Serum miR-22 as potential non-invasive predictor of poor clinical outcome in newly diagnosed, uniformly treated patients with diffuse large B-cell lymphoma: an explorative pilot study

Marchesi

Regazzo²,

Palombi

et al. 2018

J Exp Clin Cancer Res

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BackgroundDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line treatment.MicroRNAs (miRNAs) are under investigation as novel diagnostic and prognostic biomarkers in several malignancies, including malignant lymphomas. While tissue miRNAs in DLBCL patients have been extensively studied as biomarkers, only few reports to date have evaluated the role of circulating/serum miRNAs as potential prognostic factors.Here circulating/serum miRNAs, including miR-22, were investigated as potential non-invasive biomarkers, with the aim of a better prognostic stratification of DLBCL patients.MethodsMiRNAs were selected by global expression profile of serum miRNAs of DLBCL patients, The Cancer Genome Atlas (TCGA) analysis and literature research.Serum and tissues miRNA expression profile in de novo DLBCL patients, consecutively enrolled for this study, were detected by quantitative real-time polymerase chain reaction. Relative expression was calculated using the comparative Ct method. Statistical significance was determined using the Mann-Whitney rank sum and Fisher’s exact test. Survival analysis was conducted through the use of Kaplan-Meier method. Spearman’s Rho was applied to study the correlation between miRNA distributions and days to first relapse.Experimentally validated miRNA-target interactions were assessed by miRTarBase database. Negative miRNA-mRNA correlation was evaluated in TCGA DLBCL dataset. Pathway analysis was performed by the functional annotation clustering DAVID tool.ResultsWe showed a significant modulation of serum miR-22 after R-CHOP treatment compared with basal values but no difference between baseline serum miRNAs values of DLBCL patients and healthy controls. High expression level of serum miR-22 in DLBCL at diagnosis (n = 36) is associated with a worse PFS and is independent of the currently used clinical prognostic index. Integrative and pathways analysis of miR-22 identified target genes involved in different important pathways such as p53 signaling.ConclusionsOur data suggest that miR-22 is of potential interest as non-invasive biomarker to predict clinical outcome in DLBCL patients. Characterization of miR-22 pathways can pave the way to the development of targeted therapy approaches for specific subgroups of DLBCL patients.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0768-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Serum miR-22 as potential non-invasive predictor of poor clinical outcome in newly diagnosed, uniformly treated patients with diffuse large B-cell lymphoma: an explorative pilot study

Marchesi

Regazzo²,

Palombi

et al. 2018

J Exp Clin Cancer Res

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“…An aberrant miRNA signature is useful, however it is important to be able to understand the functional role of these miRNAs and how they regulate expression of their target genes, to enable clinicians to determine different therapeutic modalities for individual patients as well as response to treatment and resistance to chemotherapy. Advancement in the treatment of DLBCL includes a combination of rituximab (monoclonal antibody) with cyclophosphamide, vincristine, doxorubicin and prednisolone (R-CHOP), which has resulted in a large increase in overall survival rates, however up to 33% of patients will still eventually succumb to this disease [41,42]. Studies investigating functional diagnostic as well as prognostic biomarkers in clinical tumour tissue samples are therefore required.…”

Section: Functionally Significant Cellular Mirnas In Nhlmentioning

confidence: 99%

Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma

Bradshaw

Sutherland

Haupt

et al. 2016

Genes

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A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival.

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“…Current data show that the expression of miR222 is associated with shorter progression-free survival (PFS) in DLBCL patients treated with R-CHOP (rituximab, vincristine, doxorubicin, cyclophosphamide, and prednisone) immunochemotherapy via inducing downregulation of p27 that might facilitate cell proliferation and survival. 39 , 41 Furthermore, increased expression of miR142, miR146-5p, and miR223 and increased expression of miR146a and miR200c correlate with longer relapse and PFS in DLBCL patients treated with R-CHOP. 36…”

Section: Diffuse Large B-cell Lymphomamentioning

confidence: 94%

“… 38 It has been observed that miR155 expression is ~20–30 times higher in DLBCL cells than in normal cells. 39 There are two negative regulators of the PI3K–Akt pathway: SHIP1 and PIK3R1, which are both downregulated by miR155. In addition, miR155 downregulates BMP.…”

Section: Diffuse Large B-cell Lymphomamentioning

confidence: 99%

Abnormal microRNA expression in the course of hematological malignancies

Szymczyk¹,

Macheta²,

Podhorecka³

2018

CMAR

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Research on the carcinogenesis process is currently focused primarily on understanding its genetic basis and molecular abnormalities that may be predictive factors and therapeutic targets. It was clearly confirmed recently that microRNAs are involved in the mechanisms of leukocyte development, differentiation, and apoptosis, as well as in the pathogenesis of proliferative diseases of the hematopoietic system. Currently, research strategies allow determination of the deregulation of microRNA profiles in relation to other cytogenetic aberrations, as well as prognostic factors and primary end points. The problem of the possibility of their use as therapeutic targets is also increasingly discussed. In this article, we analyze literature data on abnormalities in microRNA expression in proliferative diseases of the hematopoietic system in the context of classic cytogenetic and molecular aberrations.

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MicroRNAs in diffuse large B-cell lymphoma

Cited by 17 publications

References 87 publications

Serum miR-22 as potential non-invasive predictor of poor clinical outcome in newly diagnosed, uniformly treated patients with diffuse large B-cell lymphoma: an explorative pilot study

Serum miR-22 as potential non-invasive predictor of poor clinical outcome in newly diagnosed, uniformly treated patients with diffuse large B-cell lymphoma: an explorative pilot study

Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma

Abnormal microRNA expression in the course of hematological malignancies

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