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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2023

Open Access 01-12-2023 | Obesity | Research

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

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

Published in: Journal of Translational Medicine | Issue 1/2023

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.
Appendix
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Metadata
Title
Analysis of circulating extracellular vesicle derived microRNAs in breast cancer patients with obesity: a potential role for Let-7a
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
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2023
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-023-04075-w

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