miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients

Lánczky, András; Nagy, Ádám; Bottai, Giulia; Munkácsy, Gyöngyi; Szabó, András; Santarpia, Libero; Győrffy, Balázs

doi:10.1007/s10549-016-4013-7

Cited by 695 publications

(645 citation statements)

References 31 publications

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“…However, this does not negate their potential cancer-related functions. In order to further explore the results, as an example, we performed survival analysis on four SDEmiRNAs unique to BRCA (absolute log2FC values > 1) by using miRpower [40]. Except hsa-mir-329–2 which is not in miRpower, the remaining three SDEmiRNAs suggest significant survival differences (log-rank p value < 0.01) between groups with under-/over-expression of each SDEmiRNA after optimizing the patient threshold (Figure S4): hsa-mir-4784 (Hazard Ratio (HR) = 1.82), hsa-mir-1262 (HR = 0.58), and hsa-mir-320c-1 (HR = 0.68).…”

Section: Resultsmentioning

confidence: 99%

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Dingerdissen

Gupta

et al. 2018

Computers in Biology and Medicine

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microRNAs (miRNAs) functioning in gene silencing have been associated with cancer progression. However, common abnormal miRNA expression patterns and their potential roles in cancer have not yet been evaluated. To account for individual differences between patients, we retrieved miRNA sequencing data for 575 patients with both tumor and adjacent nontumorous tissues from 14 cancer types from The Cancer Genome Atlas (TCGA). We then performed differential expression analysis using DESeq2 and edgeR. Results showed that cancer types can be grouped based on the distribution of miRNAs with different expression patterns between tumor and non-tumor samples. We found 81 significantly differentially expressed miRNAs (SDEmiRNAs) in a single cancer. We also found 21 key SDEmiRNAs (nine over-expressed and 12 under-expressed) associated with at least eight cancers each and enriched in more than 60% of patients per cancer, including four newly identified SDEmiRNAs (hsa-mir-4746, hsa-mir-3648, hsa-mir-3687, and hsa-mir-1269a). The downstream effects of these 21 SDEmiRNAs on cellular function were evaluated through enrichment and pathway analysis of 7,186 protein-coding gene targets mined from literature reports of differential expression of miRNAs in cancer. This analysis enables identification of SDEmiRNA functional similarity in cell proliferation control across a wide range of cancers, and assembly of common regulatory networks over cancer-related pathways. These findings were validated by construction of a regulatory network in the PI3K pathway. This study provides evidence for the value of further analysis of SDEmiRNAs as potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

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Section: Resultsmentioning

confidence: 99%

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Dingerdissen

Gupta

et al. 2018

Computers in Biology and Medicine

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“…However, due to clinical and molecular heterogeneity in different studies, as well as methodological difference regarding to reproducibility and normalization, there exists a limitation to identify the specific miRNAs as potential diagnostic and prognostic markers [27]. In addition, the number of patients enrolled in each study is generally small.…”

Section: Discussionmentioning

confidence: 99%

A three-microRNA signature as a diagnostic and prognostic marker in clear cell renal cancer: An In Silico analysis

2017

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Accumulating evidence has demonstrated that some specific miRNAs were aberrantly expressed in renal clear cell carcinoma and participated in many biological processes. The aim of this study was to investigate a panel of miRNA signature for diagnosis and prognosis of renal clear cell carcinoma (KIRC). Here, we performed a comprehensive analysis for miRNA expression profiles and corresponding clinical information of 516 KIRC patients from The Cancer Genome Atlas (TCGA). In the study, a total of 63 differentially expressed miRNAs were identified, of which 34 were up-regulated and 29 were down-regulated. We constructed a panel of three-miRNA that were significantly associated with KIRC diagnosis and KIRC patients' prognosis. The three-miRNA signature reached a sensitivity of 98.3% and a specificity of 97.2% in the diagnosis of KIRC. Using the three-miRNA signature, we classified the KIRC patients into high-risk group and low-risk group. The Kaplan- Meier curves showed that KIRC patients with high risk scores had significantly worsen overall survival (OS) and disease free survival (DFS) than KIRC patients with low risk scores. In the univariate and multivariate Cox regression analysis, three-miRNA signature was an independent prognostic factor in OS. In conclusion, the three-miRNA signature could be used as a diagnostic and prognostic biomarker in KIRC, and therefore, may help to provide significant clinical implication for the treatment of KIRC.

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“…Using miRpower 33 , we observed that lower expression of miR-29b-1 and miR-29a is associated with decreased relapse-free survival (RFS) in overall breast cancer and in patients with ER + primary tumors (Supplementary Fig. 9).…”

Section: Discussionmentioning

confidence: 99%

The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells

Muluhngwi

Alizadeh-Rad

Vittitow

et al. 2017

Sci Rep

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Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cellspecific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti-or pre-miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAMresistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics. microRNAs (miRNA, miRs) are 22 nt non-coding RNAs that recognize and bind complementary seed sequences in the 3′-UTR region of a target messenger RNA (mRNA) 1, 2 . This results in translational repression and/or transcriptional degradation of the target gene. By targeting several mRNAs, miRNAs regulate several cellular and biological processes including cell cycle, cell proliferation and cell differentiation, apoptosis, cellular respiration and glycolysis (reviewed in refs 3-6). Aberrant miRNA expression mediates disease initiation and progression in breast and other cancers 7 . Seventy percent of breast tumors express estrogen receptor alpha (ERα) implying eligibility for endocrine therapies including selective estrogen receptor modulators (SERMs), e.g., Tamoxifen (TAM), and aromatase inhibitors (AI), e.g., letrozole. The efficacy of endocrine therapy is limited by relapse in ~40% of patients 8,9 . Endocrine resistance is mediated by multiple mechanisms depending on the type of therapy used (reviewed in refs 10-14). Alterations in miRNA expression are also implicated in endocrine-resistance (reviewed in refs 15 and 16).Previously, we reported miR-29b-1 and miR-29a were downregulated by TAM in TAM-sensitive (TAM-S) MCF-7 BC cells and upregulated in TAM-resistant (TAM-R) LCC2, LCC9, and LY2 BC cells 17 . There are four miR-29 family members in the human genome: miR-29b-2 and miR-29c (chromosome 1q32.2) and miR-29b-1 and miR-29a (chromosome 7q32.3). miR-29b-1 and miR-29a are separated by ~652 bp on the same pri-miRNA transcript [18][1...

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miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients

Abstract: In summary, we established an integrated platform capable to mine all available miRNA data to perform a survival analysis for the identification and validation of prognostic miRNA markers in breast cancer.

Cited by 695 publications

References 31 publications

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

Identification of key differentially expressed MicroRNAs in cancer patients through pan-cancer analysis

A three-microRNA signature as a diagnostic and prognostic marker in clear cell renal cancer: An In Silico analysis

The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells

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