Abstract
Placenta accreta is associated with a significant risk of maternal hemorrhage, morbidity and mortality. Despite the increasing incidence of this condition, the molecular alterations associated with accreta at the utero-placental interface are poorly understood. The objective of this study was to use proteomics to characterize myometrial and placental compartments among accreta patients. We identified cesarean hysterectomy specimens from 85 accreta patients and 14 control patients with uterine atony. Uterine myometrial (n=99) and trophoblast (n=99) cells from accreta and control patients were discretely harvested by lasermicrodissection, digested, and analyzed by mass spectrometry. Protein abundances were estimated using spectral counting and significant differences in abundance from control specimens were determined. Multivariate and leave-one-out analysis were used to develop classifiers and assess performance for select comparisons. Proteomic data from 35 accreta, 44 increta, 18 percreta, and 14 control patients were compared. Unsupervised analysis demonstrated perfect clustering of proteomic data from myometrial vs placental compartments across the 198 specimens. Comparison of accreta, increta, and percreta vs control revealed 26 common placental proteins (p<0.05)and 136 common myometrial proteins (p<0.05), respectively. KRT7 and PRG2 are two notable myometrial proteins that were elevated >5-fold with p<2x10-7. Pathway analysis of the 136 accreta-associated myometrial proteins revealed immune function and cellular motility as predominant categories of dysregulation. Proteomic classifier models revealed an AUC of 0.88 for accreta vs increta/percreta and AUC of 1.0 for increta/percreta versus control. Proteomic analysis revealed more differentially expressed proteins in the myometrial compartment compared to the placental tissue among patients with accreta. This inventory of proteins warrants future investigation for diagnostic and therapeutic applications.
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