Zhirong Guo

Placenta Accreta Spectrum (PAS) is a severe obstetric disorder characterized by excessive trophoblast invasion into the uterine myometrium, leading to life-threatening hemorrhage at delivery. While closely monitored, the molecular drivers of its progression remain poorly defined, hindering predictive and therapeutic strategies. Here, we employed longitudinal quantitative proteomics on maternal plasma from five PAS patients across gestation. We identified Keratin 6A (KRT6A) as a key biomarker whose plasma levels increase with PAS progression. Immunohistochemistry confirmed the specific upregulation of KRT6A in trophoblasts at the maternal–fetal interface in PAS. Functional studies demonstrated that KRT6A overexpression significantly enhances the migration and invasion capabilities of trophoblast cell lines in vitro, without affecting proliferation or apoptosis. Integrative bioinformatics analysis linked KRT6A to the activation of the MYC signaling pathway, a known driver of invasiveness. Our data establish KRT6A as a plasma biomarker correlating with PAS severity and a functional regulator of trophoblast invasiveness. These findings suggest a novel mechanism wherein KRT6A-mediated enhancement of trophoblast invasion, potentially via MYC signaling, contributes to PAS pathogenesis. This work provides a potential circulating biomarker for monitoring PAS progression and implicates KRT6A as a candidate therapeutic target for mitigating excessive placental invasion.

Objectives: To analyze the association between pre-operational coagulation indicators and the severity of placenta accreta spectrum (PAS), as well as blood loss volume during operation. Methods: Hospitalized patients of the obstetric department in a major hospital from 2018 to 2020 who were clinically and/or pathologically diagnosed with invasive PAS were included. Univariate and multivariate logistic regression and Poisson regression models were used to quantify the association between each of the 6 coagulation indicators and PAS severity (measured by FIGO grade) as well as maternal outcomes. Results: Ninety-five patients (46 FIGO grade 2 and 49 FIGO grade 3) were included. Higher PT [adjusted OR (aOR): 5.54; 95% CI, 1.80 to 17.07] and FDP (aOR: 1.19; 95% CI, 1.01–1.42) levels were associated with an increased risk of FIGO grade 3 after adjusting for covariates. D-dimer [incidence rate ratio (IRR): 1.19; 95% CI, 1.05 to 1.35)] and FDP (IRR: 1.03; 95% CI, 1.01–1.04) levels were significantly associated with higher blood loss volume after adjusting for covariates. Conclusion: Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation of invasive PAS. The underlying mechanism for the coagulation profile of PAS patients warrants further analysis. Synopsis: Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation among invasive placenta accreta spectrum patients.