Array-based miRNA Profiling of Clear Cell Renal Cell Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12105 | GEO | 2008/10/01
SECONDARY ACCESSION(S): PRJNA113797
REPOSITORIES: GEO
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Project description:MicroRNAs (miRNAs) are short single stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. Because of the lack of corresponding data in clear renal cell carcinoma (ccRCC) we have performed genome-wide expression profiling of miRNAs using microarray analysis and quantification of specific miRNAs by TaqMan real-time RT-PCR. Matched malignant and non-malignant tissue samples from two independent 12 ccRCC sets were profiled. The microassay-based experiments identified 14 overexpressed and 20 downregultaed miRNAs in malignant samples. Expression in ccRCC tissue samples compared to matched non-malignant samples measured by RT-PCR was increased by 2.7 to 28fold for the hsa-mir-16, -452, -224, -155, and -210, but decreased by 6.2 to 96fold for hsa-mir-200b, -363, , -429, -200c, -514, and -141. No significant associations between these differentially expressed miRNAs and the clinico-pathological factors tumor stage, grade, and survival rate were found. Nevertheless, malignant and non-malignant tissue could clearly be differentiated by their miRNA profile . A combination of miR-141 and miR-155 resulted in a 96% overall correct classification of samples. The presented differential miRNA pattern provides a solid basis for further validation including functional studies. The study was performed with two independent sample sets. For each set 12 kidney tissue sample pairs were derived from adult patients undergoing radical nephrectomy at the University Hospital Charité. All tumor types were clear renal cell carcinoma. Tumor classification and stage were established according to the 2002 TNM System and the 2004 WHO Classification. Matched malignant (#NC (e.g. 2NC)) and non-malignant (#NN (e.g. 1NN)) tissue samples from two independent 12 ccRCC sets were profiled.
2010-06-25 | E-GEOD-12105 | biostudies-arrayexpress
Project description:Background/Objective: MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in metastasis of clear cell renal cell carcinomas (ccRCCs) as so-called metastamirs is still limited. Based on microRNA microarray analyses from normal (n=12) and cancerous (n=12) samples of ccRCC specimens and from bone metastases (n=9) of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between those three sample groups of ccRCC. A selected panel of 33 miRNAs, including miRNAs reported in the literature as differentially expressed in non-metastatic RCC, was validated by RT-qPCR on 57 clinical samples. 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulated miRNA expression from normal over primary tumor to metastatic tissue samples was found to be typical. 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples in comparison to normal tissue. This down-regulated expression in metastatic tissue was also present in 21 miRNAs except for miR-127 and miR-370. The altered miRNA profiles including the newly identified metastasis-associated miRNAs, the compiled predicted miRNA-target interactions, and the significant correlations of miRNAs which were either lost or newly appeared in the studied sample groups afford a solid basis for further functional analyses of individual miRNAs. In this study, microarray-based profiling was performed from 9 bone metastatic tissue samples from 9 patients with clear cell renal cell carcinoma (ccRCC). For controls, 2 bone metastatic samples from two patients with prostate carcinoma and 5 total RNA pools (2 different pools of total RNAs isolated from malignant renal tissue samples derived from different ccRCC patients; 1 pool from non-malignant renal tissue of ccRCC patients; 2 pools of total RNA both from malignant and non-malignant prostate cancer tissue) were used. In addition, matched malignant (e.g., malignant NC2) and non-malignant (e.g., non-malignant NN1) samples from two independent 12 ccRCC sets were profiled (these samples were previously analyzed on a different Platform in GSE12105). The 2002 TNM System and the 2004 WHO classification was used for staging and grading.
2013-02-26 | E-GEOD-37989 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Currently, there are no biomarkers for the diagnostic, prognostic, or predictive applications in RCC. MicroRNAs (miRNAs) are short non protein-coding RNAs that negatively regulate gene expression and have been shown to be involved in cancer. We analyzed a total of 70 matched pairs of clear cell RCC (ccRCC) and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real time PCR. We identified 166 miRNAs significantly dysregulated in ccRCC. MiR-122, miR-155 and miR-210 had the highest fold changes of overexpression while miR-200c, miR-335, and miR-218 were the most downregulated. We performed extensive bioinformatics analysis including a combinatorial analysis of previously reported miRNAs dysregulated in RCC and extensive target prediction analysis. Many miRNAs were predicted to target a number of genes involved in RCC pathogenesis. Our results showed that miRNA dysregulation in RCC can be attributed in part, to chromosomal aberrations, the co-regulation of miRNA clusters, and co-expression with host genes. We also correlated miRNA expression with clinical characteristics and found miR-155 expression was correlated with ccRCC tumor size. In conclusion, our analysis showed that a number of miRNAs are dysregulated in ccRCC and may contribute to kidney cancer pathogenesis by targeting more than one key molecule. We identified mechanisms that may contribute to miRNA dysregulation in ccRCC. Dysregulated miRNAs represent potential biomarkers for kidney cancer. We preformed a miRNA microarray on 20 pairs of matched primary clear cell renal cell carcinoma (ccRCC) and normal kidney tissue from the same patient (St. Michael's Hospital, Toronto, Canada). One matched pair was used per array for a total of 20 arrays. Microarray results were validated by quantitative real time PCR using an independent set of 50 matched pairs of ccRCC and normal kidney tissue from the same patient.
2010-07-22 | E-GEOD-23085 | biostudies-arrayexpress
Project description:To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 'diseased' (bleeding-on-probing, PD > 4 mm, and AL M-bM-^IM-% 3 mm) and 40 'healthy' (no bleeding, PD M-bM-^IM-$ 4 mm, and AL M-bM-^IM-$ 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology. The dataset comprise 200 gingival tissue samples from 86 patients with periodontitis. All samples are included in this series, but 2 where not included in the study, as they did not pass our QC. Each patient has one or more healthy and disease sample and samples can be of chronic or aggressive periodontitis type.
2014-02-05 | E-GEOD-54710 | biostudies-arrayexpress
Project description:To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 'diseased' (bleeding-on-probing, PD > 4 mm, and AL ≥ 3 mm) and 40 'healthy' (no bleeding, PD ≤ 4 mm, and AL ≤ 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology.
2014-02-05 | GSE54710 | GEO
Project description:Microglia were derived from iPSCs and treated with mimics and inhibitors of the miRNAs hsa-miR-150-5p, hsa-miR-193a-3p and hsa-miR-19b-3p. RNA-sequencing was then performed to examine the effects of up- and down-regulation of the respective miRNAs.
| EGAD00001006842 | EGA
Project description:Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Currently, there are no biomarkers for the diagnostic, prognostic, or predictive applications in RCC. MicroRNAs (miRNAs) are short non protein-coding RNAs that negatively regulate gene expression and have been shown to be involved in cancer. We analyzed a total of 70 matched pairs of clear cell RCC (ccRCC) and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real time PCR. We identified 166 miRNAs significantly dysregulated in ccRCC. MiR-122, miR-155 and miR-210 had the highest fold changes of overexpression while miR-200c, miR-335, and miR-218 were the most downregulated. We performed extensive bioinformatics analysis including a combinatorial analysis of previously reported miRNAs dysregulated in RCC and extensive target prediction analysis. Many miRNAs were predicted to target a number of genes involved in RCC pathogenesis. Our results showed that miRNA dysregulation in RCC can be attributed in part, to chromosomal aberrations, the co-regulation of miRNA clusters, and co-expression with host genes. We also correlated miRNA expression with clinical characteristics and found miR-155 expression was correlated with ccRCC tumor size. In conclusion, our analysis showed that a number of miRNAs are dysregulated in ccRCC and may contribute to kidney cancer pathogenesis by targeting more than one key molecule. We identified mechanisms that may contribute to miRNA dysregulation in ccRCC. Dysregulated miRNAs represent potential biomarkers for kidney cancer.
2010-07-22 | GSE23085 | GEO
Project description:Applying Next Generation Sequencing technique we compared the miRNA expression pattern of tumor tissue sample of 6 GPs and peritumoral region of 6 lower grade (I-II) Glioma patients, serving as control group. To determine the difference on miRNA expresion level between GBM and control cases, we performed cluster analysis on the NGS dataset of 6 replicates for each of the two goups of samples with iDEP 96 software. In order to characterize the extent of up- or downregulation, log2FC values were calculated using the iDEP.96 web tool applying the DESeq2 algorithm. On the base of that 117 known miRNAs were identified to be differentially expressed using a threshold of false discovery rate (FDR) <0.05 and fold-change> 2 during the analysis. Among them, 35 miRNAs were upregulated (log2FC > 2) and 82 miRNAs were downregulated (log2FC < -2) with biological revelance in tissue samples comparing with the control samples. To validate our results obtained by NGS, five upregulated miRNAs: hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-92b-5p, hsa-miR-10b-3p, hsa-miR-503-5p and three downregulated miRNAs: hsa-mir-383-5p, hsa-mir-490-3p, hsa-mir-1224-3p were chosen for RT-qPCR analysis. As the result of that hsa-miR-196a-5p, hsa-miR-21-3p, and hsa-miR-10b-3p was significantly upregulated while hsa-mir-383-5p and hsa-mir-490-3p was significantly downregulated, compared with those in the control samples. The other three miRNAs: hsa-miR-1224-3p, hsa-miR-92b-5p, hsa-miR-503-5p did not show significant difference between the control group and GPs.
2024-10-31 | GSE244332 | GEO
Project description:About 30% of renal cell carcinoma (RCC) patients undergoing nephrectomy experience disease recurrence. This study aimed to profile microRNAs (miRNAs) that are dysregulated in clear cell RCC (ccRCC) tumor tissues and predictive of recurrence. The expression levels of 800 miRNAs were assessed in paired tumor and normal tissues from a discovery cohort of 18 ccRCC patients via the NanoString assay platform. MiRNAs found to be differentially expressed were further examined in a validation set of 205 patients using quantitative real-time PCR. Tumor-normal data from 64 patients in The Cancer Genome Atlas were used for external validation. Results showed 28 miRNAs were consistently dysregulated in tumor tissues. Dichotomized analyses indicated patients with high levels of miR-155-5p and miR-210-3p displayed increased risk of ccRCC recurrence (HR, 2.64; 95% CI, 1.49-4.70; P=0.0009 and HR, 1.8; 95% CI, 1.04-3.12; P=0.036, respectively) and shorter median recurrence-free survival times than patients with low levels (log rank test P<0.01). A risk score was generated based on expression levels of miR-155-5p and miR-210-3p, and the trend test was significant (P for trend=0.005). Pathway analysis revealed target genes regulated by miR-155-5p and miR-210-3p were mainly enriched in inflammation-related pathways. In summary, we identified and validated multiple miRNAs dysregulated in ccRCC tissues. MiR-155-5p and miR-210-3p were predictive of ccRCC recurrence pointing to potential utility as biomarkers and underlying biological mechanisms.
2018-10-04 | GSE116251 | GEO
Project description:Background/Objective: MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in metastasis of clear cell renal cell carcinomas (ccRCCs) as so-called metastamirs is still limited. Based on microRNA microarray analyses from normal (n=12) and cancerous (n=12) samples of ccRCC specimens and from bone metastases (n=9) of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between those three sample groups of ccRCC. A selected panel of 33 miRNAs, including miRNAs reported in the literature as differentially expressed in non-metastatic RCC, was validated by RT-qPCR on 57 clinical samples. 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulated miRNA expression from normal over primary tumor to metastatic tissue samples was found to be typical. 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples in comparison to normal tissue. This down-regulated expression in metastatic tissue was also present in 21 miRNAs except for miR-127 and miR-370. The altered miRNA profiles including the newly identified metastasis-associated miRNAs, the compiled predicted miRNA-target interactions, and the significant correlations of miRNAs which were either lost or newly appeared in the studied sample groups afford a solid basis for further functional analyses of individual miRNAs.
2013-02-26 | GSE37989 | GEO