KRT6A Is a Biomarker of PAS Progression and Enhances the Invasive Ability of Trophoblast Cells

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.