MicroRNA Expression Profiling Characterize Diffuse Large B-Cell Lymphomas and Follicular Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3186-3186
Author(s):  
Anja Roehle ◽  
Kai P. Hoefig ◽  
Dirk Repsilber ◽  
Christoph Thorns ◽  
Kai O. Wesche ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Mirna Expression ◽  
Germinal Center ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Mirna Expression Profiles ◽  
Proliferation And Differentiation ◽  
Follicular Lymphomas ◽  
Large B Cell

Abstract A new and powerful tool for classification and understanding the biology of human lymphomas is microRNA (miRNA) expression profiling. MiRNAs comprise a class of approximately 1000 RNA species, which are thought to directly regulate the expression of ∼30% of the transcripts of the human genome on a posttranscriptional level. An important regulatory role of miRNAs has been implicated in biological processes such as cell proliferation and differentiation, fat metabolism, insulin secretion and hematopoiesis. Recent studies indicate that miRNAs are mechanistically involved in the development of various human malignancies and therefore represent a promising new class of biomarkers. We evaluated the miRNA expression profiles of 58 Diffuse Large B-Cell Lymphomas (DLBCL), 46 Follicular Lymphomas (FL) and 7 lymph nodes with chronic lymphadenitis. A quantitative PCR-based method was used to determine the expression levels of 157 miRNA species. The analysis was performed exclusively on FFPE tissues, which are traditionally inapt to molecular analysis. It was possible to clearly distinguish malignant and non-malignant tissues by miRNA expression patterns. We found 34 differentially expressed miRNAs by comparing DLBCL and lymph nodes, 25 miRNAs by comparing FL and lymph nodes and 55 by comparing DLBCL and FL. It was noticeable that the miRNA expression profiles of FL and lymph nodes are more similar compared to miRNA expression profiles of DLBCL. We were also interested to find out whether it is possible to classify the DLBCL cases in germinal center-like DLBCL (GCB-DLBCL) and Non-germinal center-like DLBCL (Non-GCB-DLBCL) based on miRNA expression patterns. We used the immunohistochemical classification, published by Hans et al., to identify both subgroups (Hans CP, Weisenburger DD et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103:275–282). Comparing miRNA expression profiles of GCB and Non-GCB cases of DLBCL, 8 miRNAs were found to be differentially expressed using the partial least squares discriminant analysis (PLS-DA). However, using a cross-validation approach it was not possible to predict the GCB status on the basis of miRNA expression patterns. Similar to Landgraf et al. we found a reduced miR-150 expression level in DLBCL in comparison to other closely related germinal center malignancies (Landgraf P, Ruscu M et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007; 129:1401–1414). To determine the function of miR-150, Ramos cells were transfected with anti-miR-150 and an analysis of putative target proteins was carried out. It was possible to show a regulation of transcription factor v-myb/c-myc, which plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells, by miR-150. Moreover, miRNA profiles of DLBCL from a randomized trail will be compared to survival data in the future.

Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 562-562
Author(s):  
Jean-Noel Bastie ◽  
Jean-Philippe Jais ◽  
Thierry Molina ◽  
Emmanuelle Come ◽  
Bertrand Coiffier ◽  
...  
Keyword(s):  
B Cell ◽  
Mirna Expression ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Rt Pcr ◽  
Large B Cell Lymphoma ◽  
Micro Rnas ◽  
Large B Cell

Abstract The Micro RNAs (miRNAs) are small non-coding, single-stranded RNAs that regulate the expression of genes by hybridizing the mRNA target with complementary sequences that are followed by translational repression, mRNa cleavage or destabilization. There is evidence that miRNA play an important role in carcinogenesis. Aberrant miRNA expression has been found in a variety of human malignancies including B-cell leukemias and lymphomas. The purpose of this study is to determine the miRNA expression patterns in DLBCL and their relationship with clinical characteristics and outcome. We used high throughput quantitative RT-PCR technology (Taqman Low density Arrays) to analyze the expression profile of 365 different mature miRNA in 12 Diffuse Large B-Cell Lymphoma (DLBCL) samples which had been previously characterized at the transcriptional level with Affymetrix HU133A micro-arrays. MiR-155 expression was significantly lower in the 6 samples with a Germinal Center (GC) mRNA profile than in the 6 samples with an Activated B-Cell (ABC) profile. Expression of miR-155 and of different miRNA involved in lymphoid differentiation (miR-181a, miR127) or tumour pathogenesis (cluster miR 17–92) were further evaluated in a series of 64 patients with DLBCL treated with Rituximab associated with chemotherapy (R-CHOP). 28 patients had been enrolled in the LNH98.5 GELA trial between February 1998 and February 2000 and 36 were treated with R-CHOP in GELA centers after the closure of the LNH98-5 trial, between November 2000 and June 2004. The median follow up of these patients is 69 months. Patients median age at diagnosis was 69 years (range 59–82) and 28 patients presented with an International Prognostic Index (IPI) score of more than 3. Mature miRNA expression was determined by quantitative RT-PCR with Applied Biosystems specific miRNA primer and probe sets and normalized to U6 small nuclear RNA expression. MiR-155 expression was significantly higher in patients with a lymphoma of the ABC subtype, defined on the basis of the transcriptional profile (mean delta Ct = − 3.9 in the 41 ABC samples, mean delta Ct = − 1.67 in the 23 GC samples, p<0.00001) and significantly higher in patients with a high (4 or 5) IPI score (p=0.02). A high miR-155 expression was associated with a trend towards a poorer overall survival. The expression of miR-127, miR-181a and the cluster 17–92 were not correlated with clinical outcome. These analyses are currently being extended to a larger series of patients in order to determine whether other miRNA can be used to classify DLBCL samples into ABC and GC subtypes and whether some miRNA have prognostic significance in the era of treatments combining Rituximab and chemotherapy.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic &#946;-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into &#946;-cells, resulting in enhanced &#946;-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.

Addition of Rituximab to CHOP Regimen Improves Clinical Outcome in Non-Germinal Center Type Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4725-4725
Author(s):  
Masahiro Yokoyama ◽  
Daisuke Ennishi ◽  
Kyoko Ueda ◽  
Makoto Kodaira ◽  
Shuhei Yamada ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Type 3 ◽  
Large B Cell

Abstract Background: In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified into the germinal center B-cell (GC) type, the activated B-cell (ABC) type, and the type 3 using global gene expression profiling or immunohistochemical staining. It has been reported that the GC type DLBCL showed significantly longer survival than the non-GC (ABC and the type 3) type DLBCL treated with CHOP or CHOP like regimen not using rituximab. Methods: We analyzed retrospectively the prognosis between the GC and non-GC types of DLBCL treated with R-CHOP regimen. All 50 patients with DLBCL, diagnosed between July 2003 and July 2005 were included in this study. The pathology was reviewed by hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. Patients with primary CNS- and post-transplant lymphomas were excluded. GC type or non-GC type DLBCL was determined by immunohistochemistry such as the expression patterns of CD10, BCL-6, and IRF-4 (MUM1). All patients were initially treated with six cycles of R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of R-CHOP, the patients have added radiation therapy. Results: The patients consisted of 30 GC type and 20 non-GC type DLBCL with a median age of 61.0 yr (range 31–83 yr). The median follow up of surviving patients was 24 months. CR rate between GC and non-GC types were 57.0% vs. 75.0%, p=0.186, and overall response rate were 87.0% vs. 90.0%, p=0.929, respectively. The median of progression free survival was 17.3 months vs. 19.6 months, p=0.80. There is no statistical significance difference between two groups. Conclusion: These results suggest that addition of rituximab to CHOP regimen improves clinical outcome of non-GC type DLBCL as well as GC type DLBCL.

scholarly journals MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas

2014 ◽  
Vol 170 (4) ◽  
pp. 583-591 ◽  
Author(s):  
David Velázquez-Fernández ◽  
Stefano Caramuta ◽  
Deniz M Özata ◽  
Ming Lu ◽  
Anders Höög ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Mutations ◽  
Mirna Expression Profile ◽  
Differentially Expressed ◽  
Adrenocortical Adenoma ◽  
Tumor Subtypes ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.

Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia

2015 ◽  
Vol 56 (11) ◽  
pp. 3150-3158 ◽  
Author(s):  
Francesco Maura ◽  
Giovanna Cutrona ◽  
Laura Mosca ◽  
Serena Matis ◽  
Marta Lionetti ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Mirna Expression Profiles

miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1034-1040 ◽  
Author(s):  
Santiago Montes-Moreno ◽  
Nerea Martinez ◽  
Beatriz Sanchez-Espiridión ◽  
Ramon Díaz Uriarte ◽  
Maria Elena Rodriguez ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Mirna Expression ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Test Group ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.

Immunohistochemical Reappraisal Regarding the Frequency of Primary Salivary Gland Follicular Lymphoma

2018 ◽  
Vol 27 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Hiroe Itami ◽  
Hirokazu Nakamine ◽  
Maiko Takeda ◽  
Tokiko Nakai ◽  
Tomoya Myojin ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Lymph Nodes ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Common Type ◽  
Surgical Pathology ◽  
Follicular Lymphomas ◽  
Large B Cell

Although it has been described that extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) are the most common type among primary salivary gland lymphomas (SGLs), some studies revealed that the frequency of follicular lymphomas (FLs) was as high as that of MALT lymphomas. However, it has been reported that many of these FLs may have developed in lymph nodes attached to the capsule of the glands or intraglandular lymph nodes. Clinical, histological, immunohistochemical, and cytogenetic features of 11 SGL cases, which were extracted from our surgical pathology file consisting of consecutive pathology cases, were reevaluated to further characterize whether they were actually primary SGLs. There were 3 (27%) cases of FLs, 5 (46%) cases of MALT lymphomas, and 3 (27%) cases of diffuse large B-cell lymphomas. Although all of our FL cases fulfilled the criteria of primary SGL, tumors of several FL cases were surrounded by podoplanin (by D2-40)–positive elongated vessels or linear structures indicative of nodal subcapsular sinuses (open or remnant). This finding would support the aforementioned possibility, and podoplanin staining is necessary before concluding that a FL is a primary SGL.

Neither Germinal Center (GC) vs Non-Germinal Center (Non-GC) Phenotype nor FOXP1 Expression Correlate with Outcome in AIDS-Associated Diffuse Large B-Cell Lymphoma (DLBCL): Study of Patients from AIDS Malignancies Consortium Trials 010 and 034.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2023-2023
Author(s):  
Amy Chadburn ◽  
Xia Chen ◽  
April Chiu ◽  
Elizabeth Hyjek ◽  
Wayne Tam ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Patient Population ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Hiv Positive ◽  
Ki 67 ◽  
Immunocompetent Patients

Abstract Background: Germinal center (GC) and non-germinal center (non-GC) gene expression profiles correlate with survival in immunocompetent DLBCL patients. Phenotypic expression patterns of CD10, BCL6, MUM1 and CD138 are surrogates for genetic studies with comparable survival data; CD10+, BCL6+/−, MUM1- defines GC while CD10-, BCL6-, MUM1+/− identifies the non-GC phenotype with poorer prognosis. Expression of FOXP1, a transcription factor differentially expressed in resting and activated B cells, and PRDM1/BLIMP1, a regulator of terminal B cell differentiation, are also adverse prognostic markers for DLBCL in immunocompetent patients. AIDS-associated DLBCLs from uniformly treated HIV+ patients in AMC010 (CHOP vs. CHOP-rituxan) and AMC034 (EPOCH vs. EPOCH-rituxan) were examined to determine if the GC vs. non-GC phenotype, FOXP1 expression and/or BLIMP1 expression are prognostic in this patient population. Design: Slides of 32 and 30 AIDS-associated DLBCLs from AMC010 (closed) and AMC034 (in analysis) patients, respectively, were available for FOXP1, BLIMP1, CD10, BCL6, MUM1, BCL2, Ki-67 immunohistochemistry and in situ hybridization for EBV (EBER). Antigen expression by >20% tumor cells (>10% for BLIMP1) was considered positive. GC phenotype was defined as CD10+, BCL6+/−, MUM1- while the non-GC cases were CD10-, BCL6-, MUM1+/−. Overall survival (OS) based on GC vs. non-GC phenotype was examined. FOXP1 expression was correlated with survival; BCL2, Ki-67 expression; and EBV status; BLIMP1 expression was correlated with survival in a subgroup of patients from AMC 034. Results: Of the 62 cases, 59% were MUM1, 60% BCL6, 53% CD10, 59% BCL2, 49% FOXP1, 67% BLIMP1 and 30% EBER positive. 19 (58%) cases were classified as GC and 14 as non-GC. No mean OS difference between GC and non-GC groups (p=0.74) or FOXP1+ and FOXP1- cases (p=0.8; t-test) in the AMC 010 patients; BLIMP1 expression did not correlate with survival in the subgroup of AMC 034 patients (p=0.4). GC vs. non-GC phenotype did not correlate with FOXP1 expression (p=0.1) or BLIMP1 expression (p=0.4). In addition, FOXP1 expression did not correlate with EBV positivity, BCL2, MUM1, BCL6 or CD10 expression or proliferation rate based on Ki67 (chi-square). Conclusions: AIDS-associated DLBCLs can be classified as GC and non-GC cases, but this classification does not appear to correlate with prognosis/OS in uniformly treated HIV-positive patients. Furthermore, in contrast with immunocompetent DLBCLs, FOXP1 expression also does not correlate with OS in this patient population; similarly BLIMP1 expression also does not correlate with survival in the HIV+ patient population. In addition, GC vs non-GC phenotype did not correlate with FOXP1 or BLIMP1 expression, while FOXP1 expression did not correlate with prognostic markers BCL2/Ki67 or EBV status. Thus, prognostic markers useful in immunocompetent patients with DLBCL may not be relevant for HIV positive patients, suggesting that patient immune status rather than tumor biology may be more important in predicting patient outcome.

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