MiR-155 inhibits DEPTOR in gastric diffuse large B-cell lymphoma resistant to H. pylori eradication therapy
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PROVIDER: PRJNA755999 | ENA |
REPOSITORIES: ENA
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Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182357 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182358 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182361 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182359 | GEO
Project description:miR-155-regulated mTOR and Toll-like receptor 5 in gastric diffuse large B-cell lymphoma
| PRJNA756003 | ENA
Project description:miR-200 is associated with sensitivity of gastric diffuse large B-cell lymphoma to H. pylori eradication therapy
| PRJNA756000 | ENA
Project description:Gene expression profiling was performed for 21 DLBCL patients. Based on the gene expression profile, each patient was classified into the molecular subclasses: Activated B-cell-like (ABC)/Germinal-center B-cell-like (GCB). A major clinical challenge of diffuse large B-cell lymphoma (DLBCL) is that up to 40% of patients have refractory disease or relapse after initial response to therapy, due to drug-specific molecular resistance. The purpose of the present study was to investigate microRNA (miRNA) involvement in vincristine resistance in DLBCL which was pursued by functional in vitro analysis in DLBCL cell lines and by clinical analysis of DLBCL patients treated with R-CHOP. MiR-155 was documented to be directly linked to vincristine response in DLBCL cell lines and association between miR-155 and ABC/GCB subclasses and clinical outcome was investigated in primary DLBCL samples.
2019-12-31 | GSE109027 | GEO
Project description:miRNA expression profiles in gastric diffuse large B cell lymphoma
| PRJNA756007 | ENA
Project description:Transformation of Follicular Lymphoma to Diffuse Large Cell Lymphoma: Alternative Patterns with Increased or Decreased Expression of c-myc and its Regulated genes The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all the cases of histological transformation. However, two different gene expression profiles associated with the transformation process were defined, one in which c-myc and genes regulated by c-myc showed increased expression and one in which these same genes showed decreased expression. Further, there was a striking difference in gene expression profiles between transformed DLBCL and de novo DLBCL, since the gene expression profile of transformed DLBCL was more similar to their antecedent FL than to de novo DLBCL. The study demonstrates that transformation from FL to DLBCL can occur by alternative pathways and that transformed DLBCL and de novo DLBCL have very different gene expression profiles that may underlie the different clinical behaviors of these two types of morphologically similar lymphomas.
2005-09-23 | E-SMDB-963 | biostudies-arrayexpress
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11
2002-06-27 | E-GEOD-60 | biostudies-arrayexpress