Fascin-Centred Invasive Competence in Eutopic Endometrium: A Hypothesis-Driven Narrative Review of Endometriosis Pathogenesis and Non-Surgical Biomarker Potential

Abstract

Endometriosis is a chronic, oestrogen-responsive inflammatory disease characterised by endometrial-like tissue outside the uterine cavity. Because retrograde menstruation is common, lesion establishment probably requires cellular competence and a permissive ectopic microenvironment. This hypothesis-driven narrative review evaluates fascin (FSCN1) as a candidate cytoskeletal effector and considers antecedent eutopic priming versus induction after ectopic adhesion. Functional evidence was integrated with a targeted public-data screen. Donor-level reanalysis of GSE179640 found no conclusive overall eutopic case-control difference and predominantly non-epithelial expression. Exploratory analysis of GSE203191 suggested higher FSCN1 expression within a HSPA6+ stromal subcluster in diagnosed cases, without a comparable epithelial signal or detectable increase in subcluster abundance. This small post hoc analysis remains hypothesis-generating. FSCN1 was absent from the published HECA stromal/macrophage differential-expression lists and was not prioritised by the 2023 endometriosis GWAS. The current evidence therefore argues against uniform epithelial or whole-eutopic overexpression but permits a lineage-restricted stromal state. Fascin participates in autophagy- and miR-145-sensitive invasion networks, although these pathways are pleiotropic. Validation requires cycle- and lineage-resolved tissue mapping, compositional controls, matched lesions, and direct FSCN1 perturbation. Fascin should currently be regarded as a candidate multi-marker component and preclinical target, not a validated biomarker or systemic therapeutic target.