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Analysis of circulating extracellular vesicle derived microRNAs in breast cancer patients with obesity: a potential role for Let-7a

Overview of attention for article published in Journal of Translational Medicine, March 2023
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Title
Analysis of circulating extracellular vesicle derived microRNAs in breast cancer patients with obesity: a potential role for Let-7a
Published in
Journal of Translational Medicine, March 2023
DOI 10.1186/s12967-023-04075-w
Pubmed ID
Authors

Ines Barone, Luca Gelsomino, Felice Maria Accattatis, Francesca Giordano, Balazs Gyorffy, Salvatore Panza, Mario Giuliano, Bianca Maria Veneziani, Grazia Arpino, Carmine De Angelis, Pietro De Placido, Daniela Bonofiglio, Sebastiano Andò, Cinzia Giordano, Stefania Catalano

Abstract

The incidence of obesity, a known risk factor for several metabolic and chronic diseases, including numerous malignancies, has risen sharply in the world. Various clinical studies demonstrate that excessive Body Mass Index (BMI) may worsen the incidence, prognosis, and mortality rates of breast cancer. Thus, understanding the link tying up obesity and breast cancer onset and progression is critically important, as it can impact patients' survival and quality of life. Recently, circulating extracellular vesicle (EV) derived miRNAs have attracted much attention for their diagnostic, prognostic and therapeutic potential in oncology research. Although the potential role of EV-derived miRNAs in the early detection of breast cancer has been repeatedly mentioned, screening of miRNAs packaged within serum EVs has not yet been reported in patients with obesity. Circulating EVs were isolated from normal weight (NW), and overweight/obese (OW/Ob) breast cancer patients and characterized by Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and protein marker expression. Evaluation of EV-associated miRNAs was conducted in a screening (RNA-seq) and a validation (qRT-PCR) cohort. Bioinformatic analysis was performed to uncover significantly enriched biological processes, molecular functions and pathways. ROC and Kaplain-Meier survival analyses were used for clinical significance. Comparison of serum EV-derived miRNAs from NW and OW/Ob patients detected seven differentially expressed miRNAs (let-7a-5p, miR-122-5p, miR-30d-5p, miR-126-3p, miR-27b-3p, miR-4772-3p, and miR-10a-5p) in the screening cohort. GO analysis revealed the enrichment of protein phosphorylation, intracellular signal transduction, signal transduction, and vesicle-mediated transport among the top biological processes. In addition, the target genes were significantly enriched in pathways related to PI3K/Akt, growth hormones, and insulin signalings, which are all involved in obesity-related diseases and/or breast cancer progression. In the validation cohort, qRT-PCR confirmed a significant down-regulation of EV-derived let-7a in the serum of OW/Ob breast cancer patients compared to NW patients. Let-7a levels also exhibited a negative correlation with BMI values. Importantly, decreased let-7a miRNA expression was associated with higher tumor grade and poor survival in patients with breast cancer. These results suggest that serum-EV derived miRNAs may reflect a differential profile in relation to a patient's BMI, which, once validated in larger cohorts of patients, could provide insights into novel specific biomarkers and innovative targets to prevent the progression of obesity-mediated breast cancer.

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X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 12%
Student > Bachelor 3 12%
Unspecified 1 4%
Other 1 4%
Student > Doctoral Student 1 4%
Other 2 8%
Unknown 14 56%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 16%
Medicine and Dentistry 2 8%
Unspecified 1 4%
Computer Science 1 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Other 2 8%
Unknown 14 56%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 April 2023.
All research outputs
#15,913,663
of 25,634,695 outputs
Outputs from Journal of Translational Medicine
#2,062
of 4,692 outputs
Outputs of similar age
#207,825
of 423,644 outputs
Outputs of similar age from Journal of Translational Medicine
#58
of 126 outputs
Altmetric has tracked 25,634,695 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,692 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has gotten more attention than average, scoring higher than 53% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 423,644 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 126 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.