Analysis of circulating microRNAs in adrenocortical tumours
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Diana Szabo
PROVIDER: E-GEOD-49674 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Differential diagnosis of adrenocortical adenoma and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumours is entirely different. Circulating microRNAs are promising biomarker candidates of malignancy in several tumours. In the present study we investigate circulating microRNAs in adrenocortical tumours and to evaluate their potential applicability as biomarkers of malignancy.
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Project description:Analysis of circulating microRNAs in adrenocortical tumours
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Project description:Circulating microRNAs have recently emerged as a new class of promising non-invasive cancer biomarkers. The purpose of this study was the identification by a high-throughput approach (miRNA microarray) of circulating miRNAs associated with breast cancer-derived distant metastasis. To achieve this goal, we resorted to archival plasma samples collected from patients in the control arm of a randomized clinical trial on stage I breast cancer. We compared plasma miRNA levels in patients that developed distant metastasis after a radical or conservative surgery and in those long-term disease-free. Microarray results were technically and independently validated by Real Time PCR. Subsequent in vitro, in vivo and in silico analyses were performed to investigate the miRNA biological/clinical significance in relation with breast cancer progression. We demonstrated that high circulating miR-1246 levels were associated to distant metastasis and that high tissue expression of this miRNA was correlated with unfavorable outcome in ER+HER2- breast cancer patients. In addition, miR-1246 expression was also found to be related with stem-like features. 64 samples (32 patients with metastasis and 32 patients with no metastasis) were considered from a total of 208 hybridized samples collected between 1987 and 2004 (including 94 paired samples according to tumor ER status, age at drawing, drawing year, time from surgery, 7 additional samples from 'no evidence of disease' (NED) patients, 10 references, 1 healthy donor and 2 replicated samples)
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Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures
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