Integrating circulating microRNAs with epidemiological factors enhances breast cancer detection across subtypes: screening phase [miRNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE319901 | GEO | 2026/02/20
REPOSITORIES: GEO
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Project description:Integrating circulating microRNAs with epidemiological factors enhances breast cancer detection across subtypes: screening phase [miRNA-Seq]
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Project description:This study represents the validation phase of circulating microRNAs associated with breast cancer detection within the MCC-Spain study. A total of 444 participants (127 cancer-free controls and 317 breast cancer cases) were included. Cases were stratified into molecular subtypes (Luminal A, Luminal B, HER2-positive, and Basal-like) according to St. Gallen criteria. A panel of 46 candidate miRNAs was quantified in serum samples using RT-qPCR (miRCURY LNA technology). Two endogenous miRNAs (let-7d-5p and let-7i-5p) were used for normalization. Differential expression and predictive modeling were performed using normalized and log₂-transformed expression values. This dataset supports subtype-specific and overall breast cancer detection models integrating molecular and epidemiological factors.
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Project description:In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery During drug discovery and development, the early identification of adverse effects is expected to reduce costly late stage failures of candidate drugs. As risk/safety assessment takes place rather late during the development process and due to the limited predictivity of animal models to the human situation, modern unbiased high-dimensional biology read-outs are sought, such as molecular signatures of in vivo response using high-throughput cell-based assays. In this theoretical proof-of-concept we provide findings of an in-depth exploration of a single chemical core structure. Via transcriptional profiling we identified a subset of close analogs which commonly down-regulate tubulin genes across cellular contexts, suggesting possible spindle poison effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test) and the identification of a characteristic aggregate-formation phenotype via exploratory high content imaging validated the inititial findings. SAR analysis triggered the synthesis of a new set of compounds and allowed us to extend the series showing the genotoxic effect. We demonstrate the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery. We share our thoughts on how this approach may be incorporated into drug development strategies.
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