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Role of microRNAs and microRNA machinery in the pathogenesis of Diffuse large B-cell Lymphomas

ABSTRACT: We performed miRNA expression profiling in a series of de novo DLBCLs, transformed DLBCLs and non-neoplastic lymph nodes using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 470 miRNAs was used to determine miRNA expression profiles in 45 DLBCL cases (32 de novo and 13 transformed) and 10 lymph nodes. To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.

ORGANISM(S): Homo sapiens

SUBMITTER: Stefano Caramuta Pinar Akçakaya Rose-Marie Amini Catharina Larsson Xie Hong Deniz Özata Gunilla Enbland Mattias Berglund Weng-Onn Lui Patrik Georgii-Hemming Linkiat Lee

PROVIDER: E-GEOD-42906 | ArrayExpress | 2014-01-27

SECONDARY ACCESSION(S): GSE42906PRJNA183858

REPOSITORIES: GEO, ArrayExpress

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Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma.

Caramuta S S Lee L L Ozata D M DM Akçakaya P P Georgii-Hemming P P Xie H H Amini R-M RM Lawrie C H CH Enblad G G Larsson C C Berglund M M Lui W-O WO

Blood cancer journal 20131011

Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA ...[more]

PMID: 24121164

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Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma.

Project description:Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL.

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MicroRNA Expression Profiles Associated with Mutational Status and Survival in Malignant Melanoma

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Project description:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that great efforts had been made in to build up molecular and immunophenotypic subgroups that could relatively accurate indicate prognosis and give clue to therapy. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, especially in Asian patients. Here, we studied 232 cases of de novo DLBCL in East China to investigate the prevalence and clinicopathological features of CD30-positive DLBCL using a panel of immunohistochemical markers. Applying a >0% threshold, CD30 was expressed in approximately 12% patients with Epstein-Barr virus (EBV) negative DLBCL, affecting younger people and showing a lower frequency of BCL2 expression and MYC/BCL2 co-expression. Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on BCL2+ DLBCL or DLBCL with MYC/BCL2 co-expression. Moreover, CD30 could express in CD5+ DLBCL. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes in a Chinese population. Further studies with larger samples should be performed to investigate the function of CD30 expression in BCL2+ DLBCLs, DLBCLs with MYC/BCL2 co-expression, and CD5+ DLBCLs, and to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy.

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Characteristics of CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors.

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Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification.

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microRNA expression signatures of imatinib-treated and non-treated gastrointestinal stromal tumors

Project description:We performed microRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib-treated and non-treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed microRNAs among imatinib-treated and non-treated groups were identified using SAM analysis. Agilent microarray platform with probes matching 903 human microRNAs was used to determine miRNA expression profiles in 34 GISTs (19 imatinib-treated and 15 non-treated). Re-analysis of GSE45901 for 17 imatinib-treated GISTs. To validate the microarray platform, the expression levels of selected microRNAs were evaluated using qRT-PCR.

2015-08-01 | E-GEOD-63159 | ArrayExpress

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