Intrahepatic miRNA/mRNA expression in non-responders to pegylated interferon plus ribavirin combination therapy for chronic hepatitis C (miRNA microarray data)
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE45179 | GEO | 2014/05/15
SECONDARY ACCESSION(S): PRJNA193148
REPOSITORIES: GEO
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Project description:Despite advance in interferon-based treatment for chronic hepatitis C, difficult-to-treat patients remain in existence yet. To identify key genes involved in difficult-to-treat characteristics, gene expression patterns of miRNA and RNA were analyzed by profiling pretreatment liver tissues from five sustained virological responders (SVR), three relapsers (R) and four non-responders (NR). Expression levels of miRNA and mRNA were compared between SVR/R and NR groups by using microarray, respectively. Quantitative real-time reverse-transcriptase polymerase chain reaction and statistical analyses validated genes with significantly differential expression levels in 50 liver tissues: proliferation-, inflammation- and anti-apoptosis-related mRNA expression levels increased significantly in NR, compared to SVR/R. Of miRNA with significantly differential expression levels on microarray, several miRNA were correlated inversely with those significant mRNA. In vitro studies by using miRNA inhibitors and mimics verified the inverse correlation between the miRNA and mRNA. These findings enhance our understanding of the difficult-to-treat molecular mechanism and identification of target molecules for novel treatments.
2014-05-14 | GSE42697 | GEO
Project description:Despite advance in interferon-based treatment for chronic hepatitis C, difficult-to-treat patients remain in existence yet. To identify key genes involved in difficult-to-treat characteristics, gene expression patterns of miRNA and RNA were analyzed by profiling pretreatment liver tissues from five sustained virological responders (SVR), three relapsers (R) and four non-responders (NR). Expression levels of miRNA and mRNA were compared between SVR/R and NR groups by using microarray, respectively. Quantitative real-time reverse-transcriptase polymerase chain reaction and statistical analyses validated genes with significantly differential expression levels in 50 liver tissues: proliferation-, inflammation- and anti-apoptosis-related mRNA expression levels increased significantly in NR, compared to SVR/R. Of miRNA with significantly differential expression levels on microarray, several miRNA were correlated inversely with those significant mRNA. In vitro studies by using miRNA inhibitors and mimics verified the inverse correlation between the miRNA and mRNA. These findings enhance our understanding of the difficult-to-treat molecular mechanism and identification of target molecules for novel treatments. Moderated t-statistics based on the empirical Bayes approach were performed to identify mRNA or miRNA differentially expressed between SVRs/relapses and NVRs using the “limma” package from BioConductor software (http://www.bioconductor.org/) under R statistical software version 2.12.1 (http://www.r-project.org/). Because of multiple hypothesis testing, p values were adjusted by the Benjamini-Hochberg false discovery rate (FDR) method. Related miRNA expression data are in GSE45179.
2014-05-14 | E-GEOD-42697 | biostudies-arrayexpress
Project description:Despite advance in interferon-based treatment for chronic hepatitis C, difficult-to-treat patients remain in existence yet. To identify key genes involved in difficult-to-treat characteristics, gene expression patterns of miRNA and RNA were analyzed by profiling pretreatment liver tissues from five sustained virological responders (SVR), three relapsers (R) and four non-responders (NR). Expression levels of miRNA and mRNA were compared between SVR/R and NR groups by using microarray, respectively. Quantitative real-time reverse-transcriptase polymerase chain reaction and statistical analyses validated genes with significantly differential expression levels in 50 liver tissues: proliferation-, inflammation- and anti-apoptosis-related mRNA expression levels increased significantly in NR, compared to SVR/R. Of miRNA with significantly differential expression levels on microarray, several miRNA were correlated inversely with those significant mRNA. In vitro studies by using miRNA inhibitors and mimics verified the inverse correlation between the miRNA and mRNA. These findings enhance our understanding of the difficult-to-treat molecular mechanism and identification of target molecules for novel treatments. Moderated t-statistics based on the empirical Bayes approach were performed to identify miRNA differentially expressed between SVRs/relapses and NVRs using the M-bM-^@M-^\limmaM-bM-^@M-^] package from BioConductor software (http://www.bioconductor.org/) under R statistical software version 2.12.1 (http://www.r-project.org/). Because of multiple hypothesis testing, p values were adjusted by the Benjamini-Hochberg false discovery rate (FDR) method. Related mRNA expression data are in GSE42697.
2014-05-15 | E-GEOD-45179 | biostudies-arrayexpress
Project description:We report the aqueous humor-derived exosomal miRNA expression profiles from CSC patients and cataract patients as control, and with analysis by anti-VEGF treatment responders (CSC-R) and non-responders (CSC-NR).
2023-08-08 | GSE227142 | GEO
Project description:Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ?10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML. Dasatinib pre-treatment and 1-yr post-treatment samples from 3 responders (R) or 4 non-responders (NR) chronic myeloid leukemia (CML) patients were investigated. We analyzed expression of Pre-treatment R vs. Pre-treatment NR; Pre-treatment R vs. Post-treatment NR; Pre-treatment NR vs. Post-treatment NR.
2013-07-31 | E-GEOD-33224 | biostudies-arrayexpress
Project description:Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ≤10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML. Dasatinib pre-treatment and 1-yr post-treatment samples from 3 responders (R) or 4 non-responders (NR) chronic myeloid leukemia (CML) patients were investigated. We analyzed expression of Pre-treatment R vs. Pre-treatment NR; Pre-treatment R vs. Post-treatment NR; Pre-treatment NR vs. Post-treatment NR.
2013-07-31 | E-GEOD-33288 | biostudies-arrayexpress
Project description:Introduction: Systems vaccinology is a novel approach to predict immune response in vaccines. We have used a systems biology approach to identify early gene ‘signatures’ that predicted viral load control after analytical therapy interruption (ATI) in HIV-1 infected patients vaccinated with a dendritic cell-based (DC) HIV-1 vaccine. Methods: Frozen post-vaccination PBMC samples from participants of a previously published DC vaccine (DCV2) clinical trial were used for the study. mRNA and miRNA were extracted and gene expression was determined by microarray method. Differential gene expression analysis was performed on both mRNA and miRNA between responders (> 1 log10 copies/mL drop of VL after 12 weeks of ATI) and non-responders (<= 1 log10 copies/mL drop in VL at week 12 of ATI). Gene set enrichment analysis (GSEA) was carried out with the hallmark gene sets of the Broad Institute on the mRNA data. After the stand-alone analyses of mRNA and miRNA we performed an additional GSEA with gene sets defined by the genes regulated by significantly differentially expressed miRNAs. Statistical analysis was done using R and the GSEA software of the Broad Institute. Results: There were 15 responders and 20 non-responders. No differentially expressed mRNAs were observed between responders and non-responders. As compared with non-responders, responders showed an up-regulation of gene sets corresponding to TNF- alpha signaling via the NFkB pathway, inflammatory response, coagulation, the complement system, Il6 and Il2 JAK-STAT signaling, or reactive oxygen-species pathways were up-regulated, and a down-regulation of gene sets corresponding to E2F targets, oxidative phosphorylation, or interferon alpha response. We found 9 differentially expressed miRNAs between responders and non-responders: miR-32-3p, miR-185-3p, miR-223-3p, miR-500b-3p, miR-550a-3p, miR-1183, miR-1184, miR-4455, and miR-8063. Twelve Broad hallmark gene sets that were significantly deregulated in the GSEA showed significant overlap with genes regulated by one or more of these miRNAs, 10 of them with genes regulated by miR-223-3p. We also observed that the expression of genes regulated by miR-223-3p, miR-1183 and miR-8063 was significantly down-regulated in responders as compared with non-responders. Conclusions: Deregulation of certain gene sets related to inflammatory processes seems fundamental in viral control during ATI. miR-223-3p may be one of the miRNAs that fine tune part of these processes.
2021-08-04 | E-MTAB-10414 | biostudies-arrayexpress
Project description:Introduction: Systems vaccinology is a novel approach to predict immune response in vaccines. We have used a systems biology approach to identify early gene ‘signatures’ that predicted viral load control after analytical therapy interruption (ATI) in HIV-1 infected patients vaccinated with a dendritic cell-based (DC) HIV-1 vaccine. Methods: Frozen post-vaccination PBMC samples from participants of a previously published DC vaccine (DCV2) clinical trial were used for the study. mRNA and miRNA were extracted and gene expression was determined by microarray method. Differential gene expression analysis was performed on both mRNA and miRNA between responders (> 1 log10 copies/mL drop of VL after 12 weeks of ATI) and non-responders (<= 1 log10 copies/mL drop in VL at week 12 of ATI). Gene set enrichment analysis (GSEA) was carried out with the hallmark gene sets of the Broad Institute on the mRNA data. After the stand-alone analyses of mRNA and miRNA we performed an additional GSEA with gene sets defined by the genes regulated by significantly differentially expressed miRNAs. Statistical analysis was done using R and the GSEA software of the Broad Institute. Results: There were 15 responders and 20 non-responders. No differentially expressed mRNAs were observed between responders and non-responders. As compared with non-responders, responders showed an up-regulation of gene sets corresponding to TNF- alpha signaling via the NFkB pathway, inflammatory response, coagulation, the complement system, Il6 and Il2 JAK-STAT signaling, or reactive oxygen-species pathways were up-regulated, and a down-regulation of gene sets corresponding to E2F targets, oxidative phosphorylation, or interferon alpha response. We found 9 differentially expressed miRNAs between responders and non-responders: miR-32-3p, miR-185-3p, miR-223-3p, miR-500b-3p, miR-550a-3p, miR-1183, miR-1184, miR-4455, and miR-8063. Twelve Broad hallmark gene sets that were significantly deregulated in the GSEA showed significant overlap with genes regulated by one or more of these miRNAs, 10 of them with genes regulated by miR-223-3p. We also observed that the expression of genes regulated by miR-223-3p, miR-1183 and miR-8063 was significantly down-regulated in responders as compared with non-responders. Conclusions: Deregulation of certain gene sets related to inflammatory processes seems fundamental in viral control during ATI. miR-223-3p may be one of the miRNAs that fine tune part of these processes.
2021-08-04 | E-MTAB-10421 | biostudies-arrayexpress
Project description:The goal of this work is to find robust predictors of tumor response to preoperative chemoradiotherapy in LARC patients. Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumour response to pCRT is not uniform and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression is associated with response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression was analyzed using one-color microarrays technique comparing signatures between responders (R) and not responders(NR), as measured by tumour regression grade (TRG). Two groups composed by 38 “exploration cohort” and 21 “validation cohort” LARC patients respectively were considered, for a total of 32 NR and 27 R patients. In the first cohort, SAM Two Class identified 256 genes and 29 miRNAs differentially expressed between NR and R. The anti-correlation analysis showed that the same 8 miRNA interacted with different networks of transcripts. The miR-630 appeared only with NR patients and was anti-correlated with a single transcript: RAB5B. After PAM, resulted as strong predictors of tumour responsen the following 8 transcripts: TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7 and GTSE1. Using this gene set, an unsupervised cluster analysis applied to the second cohort assigned the patients to the NR or R group with 85.7% accuracy with a sensitivity of 90% and a specificity of 82%. All the three parametres reached 100% when the two cohorts were considered together.
2016-04-22 | GSE68204 | GEO
Project description:Phenotypic and immunogenetic characteristics of NK cells have been recently associated with treatment outcome of HCV infected patients. However, thus far, no global NK patterns predictive of response to antiviral therapy in HCV infection have been identified. We here analyzed phenotypic and transcriptional characteristics of NK cells derived from prospectively followed patients with chronic HCV infection prior to treatment with PEG-IFN/RBV. The results report that the pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients and surprisingly overlapped with the genomic profile of NK cells from healthy donors and from patients who spontaneously cleared the virus (SR). The treatment outcome was associated with differential surface expression of NKp30 and NKG2D and with the transcriptional expression of molecules involved in post-transcriptional modifications of RNA/protein trafficking and HLA class II signaling. With the development of a highly stringent prediction model (LOOCV p value < 0.00001) we identified a 33 gene signature whose expression predicted with 100% accuracy the outcome of IFN based treatment. None of the genes found to differentiate patients with SVR from NR were related to the IL28B polymorphism. Neither an IL28B CC homozygosis was significantly and clearly associated with SVR in our series of patients. Thus, NK cells are associated to different HCV disease courses and response to treatment and the NK cell evaluation in HCV patients might provide a comprehensive explanation of useful determinants of clinical response in HCV-infected patients subjected to treatment regimens that have IFN as their backbone.
2015-10-01 | GSE51941 | GEO