Project description:BackgroundExtracellular vesicles (EVs), ubiquitously released by blood cells, facilitate intercellular communication. In cancer, tumor-derived EVs profoundly affect the microenvironment, promoting tumor progression and raising the risk of recurrence. These EVs contain miRNAs (EV-miRNAs), promising cancer biomarkers. Characterizing plasma EVs and identifying EV-miRNAs associated with breast cancer recurrence are crucial aspects of cancer research since they allow us to discover new biomarkers that are effective for understanding tumor biology and for being used for early detection, disease monitoring, or approaches to personalized medicine. This study aimed to characterize plasma EVs in breast cancer (BC) patients and identify EV-miRNAs associated with BC recurrence.MethodsThis retrospective observational study included 24 BC patients divided into recurrence (n= 11) and non-recurrence (n= 13) groups. Plasma EVs were isolated and characterized. Total RNA from EVs was analyzed for miRNA expression using NanoString's nCounter® miRNA Expression Assays panel. MicroRNA target prediction used mirDIP, and pathway interactions were assessed via Reactome.ResultsA stronger presence of circulating EVs was found to be linked with a less favorable prognosis (p = 0.0062). We discovered a distinct signature of EV-miRNAs, notably including miR-19a-3p and miR-130b-3p, which are significantly associated with breast cancer recurrence. Furthermore, miR-19a-3p and miR-130b-3p were implicated in the regulation of PTEN and MDM4, potentially contributing to breast cancer progression.A notable association emerged, indicating a high concentration of circulating EVs predicts poor prognosis (p = 0.0062). Our study found a distinct EV-miRNA signature involving miR-19a-3p and miR-130b-3p, strongly associated with disease recurrence. We also presented compelling evidence for their regulatory roles in PTEN and MDM4 genes, contributing to BC development.ConclusionThis study revealed that increased plasma EV concentration is associated with BC recurrence. The prognostic significance of EVs is closely tied to the unique expression profiles of miR-19a-3p and miR-130b-3p. These findings underscore the potential of EV-associated miRNAs as valuable indicators for BC recurrence, opening new avenues for diagnosis and treatment exploration.

Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development. Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

Project description:Background: Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. In maternal obesity, miRNAs in bEVs are deregulated, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of obese mothers and their potential impact on breastfed infants. Methods: We recruited healthy nursing mothers who were either obese (BMI≥30) or lean (BMI<25) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior six months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find deregulated miRNAs in bEVs of obese mothers compared to lean mothers. Results: We included 65 nursing mothers: 47 lean and 18 obese mothers based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of general EV markers. Out of 37 EV markers, CD326 was the most highly expressed marker in bEVs. From miRNA analysis using NanoString, we found that the most abundant miRNAs include miR-30b-5p, miR-494-3p, and let-7 families, and the list of top 10 miRNAs was not different between lean and obese mothers. Target genes of the top 10 miRNAs were associated with the EGFR, ErbB, and FoxO signaling pathway. Nineteen miRNAs were deregulated in bEVs of obese mothers (adjusted p < 0.05 cut-off), including miR-575, miR-548g-3p, miR-582-3p, and miR-652-5p. The target genes of these miRNAs are associated with lipid metabolism, inflammatory diseases, and nervous/cardiovascular system development. Conclusion: In this study, we demonstrated altered miRNAs in bEVs of obese mothers and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.

Dataset Information

EV-miRNAs as biomarkers of breast cancer recurrence

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets