77 - Serum exosomal microRNA pathway activation in Placenta Accreta Spectrum (PAS) pathophysiology and detection

Saturday, February 11, 2023

8:15 AM – 8:30 AM

Location: Room 3022, Moscone West, Level 3

Objective:
Placenta Accreta Spectrum (PAS) disorders are a complex range of placental pathologies associated with significant maternal morbidity and mortality. Diagnosis of PAS relies on ultrasonographic findings with a limited positive predictive value. Exosomal microRNA (miR) are small RNA molecules which reflect the cellular processes of origin tissues. We aimed to explore exosomal miR expression to understand PAS pathology and clinical utility for PAS detection.

Study Design: This study was a prospective cohort analysis between two large academic institutions from 2011-2022. Plasma specimens were collected from patients with suspected PAS, placenta previa or repeat cesarean section. Exosomes were quantified and characterized by flow cytometry and western blot. MiR were assessed by PCR array and targeted single quantification. MiR pathway analysis was performed using Ingenuity® software. Placental biopsies were taken of all groups and analyzed by PCR and whole cell ELISA. ROC univariate analysis was performed for microRNA prediction of PAS. Clinically relevant outcomes were collected from available electronic medical records.

Results: Plasma specimens were analyzed from a total of 120 subjects (60 PAS, 30 placenta previa and 30 control). Isolated serum exosomes had a mean size of 71.5 nm and were ten times greater in PAS specimens (20 vs 2 particles/frame). Protein expression of exosomes were positive for ICAM-1, Flotilin, Annexin and CD9. MiR analysis showed increased detection of three miRs (mir-92/103/192) in patients with PAS. Pathway interaction assessment revealed differential regulation of p53 signaling in PAS and ERBB2/HER2 in control specimens, these findings were subsequently confirmed in placental protein analysis. Placental miR paralleled serum exosomal miR expression. Biomarker assessment of PAS-signature miR had an AUC=0.81 (p < 0.001, 95% CI [0.73-0.89]) with a sensitivity and specificity of 89.2% and 80%, respectively.

Conclusion: In this large cohort, plasma exosomal miR assessment revealed differentially expressed pathways in PAS and served as a potential biomarker for the detection of PAS.

Primary & Presenting Author(s)

Jessian L. Munoz, MD, PhD, MPH (he/him/his)

Clinical Assistant Professor
Baylor College of Medicine
Houston, TX, United States

Coauthor(s)

Brett D. Einerson, MD, MPH (he/him/his)

Assistant Professor, Director of The Utah Placenta Accreta Program
University of Utah Health
Salt Lake City, Utah, United States
KI

Kayla E. Ireland, MD, MSCI

Assistant Professor
University of Texas Health Science Center at San Antonio
San Antonio, TX, United States
RS

Robert M. Silver, MD

University of Utah Health
Salt Lake City, Utah, United States
SP

Sureshkumar Pillai, PhD

University of Texas Health San Antonio
San Antonio, Texas, United States
LS

Lauren Sherman, BS

Rutgers New Jersey Medical School
Newark, New Jersey, United States
PR

Pranela Rameshwar, PhD

Rutgers New Jersey Medical School
Newark, New Jersey, United States
Egle Bytautiene Prewit, MD, PhD (she/her/hers)

UT Health San Antonio
San Antonio, Texas, United States
Patrick S. Ramsey, MD,MPH (he/him/his)

Professor, OB/GYN
University of Texas Health Sciences Center at San Antonio
San Antonio, Texas, United States