Extracellular Vesicles-Based
Biomarkers Represent a Promising
Liquid Biopsy in Endometrial
Cancer
Carolina Herrero Filgueira, PhD student, Translational Medical
Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS)
Introduction
CTCs cfDNA EVs
EVs --> Heterogeneous group of cell-derived membranous structures comprising exosomes, microvesicles and apoptotic bodies
Mechanism for intercellular communication. Messengers in tumor progression and metastasis (pre-metastatic niche formation)
EVs as biomarkers
Introduction
Gustafson D. et al., Front Cardiovasc Med. 2017 Nov 9; 4: 71.
ISOLATION METHODS
Ultracentrifugation
Ultrafiltration
SEC
Precipitation-Based EVs
Isolation
Microfluidics-Based EVs Capture
Introduction
Pin Li et al.,Theronostic. 2017 Jan 26;7(3):789-804 Monguió-Tartajada M. et al., Cell Mol Lif Sci. 2019 Jun;76(12):2369-2382
Immunoaffinity-Based EVs Capture
Introduction
Introduction
Williams C., et al,. J Extracell Vesicles. 2018 Mar 7;7(1): 1442985
EVs Precipitated
5 min 4oC 15 min 16000xg 4oC
Methodology
100-500µl
High
COSTS
SPECIFICITY
SAMPLE
TIME
Economical
ExoGAG Competitors
20 min >1h
Low
>1ml
Specific equipment
Application of ExoGAG technology
- EC is the most common neoplasm of the female genital tract in the developed world
- Recurrent EC --> poor prognosis --> L1CAM and ANXA2 --> Need for a biomarker with high sensitivity and/or specificity
ENDOMETRIAL CANCER (EC)
Adapted from Siegel RL. et al., CA Cancer J Clin. 2018 Jul; 68(4): 284-296
Results
EVs isolated from Hec1A endometrial cancer cells
- Characterization - Ultracentrifugation vs. ExoGAG
Herrero et al. Cancers. 2019 Dec 12; 11 (12)
EVs isolated from plasma samples
Results
- Characterization - ExoGAG vs ExoQuick and ExoSpin
Herrero et al. Cancers. 2019 Dec 12; 11 (12)
ANXA2 levels are increased in circulating EVs of EC patients
Results
Herrero et al. Cancers. 2019 Dec 12; 11 (12)
ANXA2 levels in purified EVs from EC patients showed diagnostic value and correlated with tumor aggressiveness
Results
- Patients with non-endometrioid tumors and high risk of recurrence had higher ANXA2 levels in purified EVs
- Clinical value of EV-associated ANXA2
Herrero et al. Cancers. 2019 Dec 12; 11 (12)
BASELINE (SURGERY) N= 41 EC
N= 20 CTRL
Conclusions
ExoGAG is a robust and highly efficient technology for the isolation of EVs from different biological fluids such as conditioned culture medium and plasma.
ExoGAG technology demonstrated an optimal performance for the clinical implementation of EVs
purified from plasma of EC patients.
The specific expression of the EC biomarkers ANXA2 in the isolated EVs improved their specificity and sensibility as liquid biopsy.
High ANXA2 levels in plasmatic EVs were associated with non-endometrioid tumors and high risk of recurrence tumors, evidencing the potential use of EV-based ANXA2 expression as a diagnostic and prognostic liquid biopsy biomarker in EC.
Acknowledgments
Miguel Abal Posada Lorena Alonso Alconada
Alba Ferreirós López Carlos Casas Arozamena
Alexandre de la Fuente González
VHIR
Eva Colás Antonio Gil-Moreno
INA
Victor Sebastián Manuel Arruebo
MD Anderson Cancer Center
Gema Moreno-Bueno
Specials thanks to all patients who participated in
the study
CHUS Ana Vilar
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