Pretreatment ACTN4 and SARS2 protein expression are associated with neoadjuvant chemotherapy response and prognosis in high-grade serous ovarian carcinoma: a retrospective exploratory study

High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive subtype of epithelial ovarian cancer, accounting for the highest mortality among gynecologic malignancies. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is a standard treatment for advanced HGSOC, yet responses to NACT vary significantly among patients. The Chemotherapy Response Score (CRS)—a histopathological assessment of treatment response—is clinically valuable, but reliable predictive biomarkers remain elusive. We retrospectively analyzed 159 HGSOC patients treated with NACT and subsequent IDS between 2013 and 2022. CRS was assigned to postoperative specimens as: CRS1 (no/minimal response), CRS2 (partial response), or CRS3 (complete/near-complete response). Immunohistochemistry (IHC) was used to evaluate ACTN4 and SARS2 protein expression in pre-NACT biopsy samples. Results showed that CRS3 patients had significantly longer progression-free survival (PFS) and overall survival (OS) than CRS1/2 patients ( P < 0.001). High ACTN4 or SARS2 expression was associated with lower CRS3 rates (8% vs. 35.2% and 12.2% vs. 28.6%, respectively; both P < 0.001), with the lowest CRS3 rate (5.1%) observed when both proteins were highly expressed (vs. 37.5% in the dual-low group; P < 0.001). Moreover, low ACTN4 expression correlated with longer OS, while low SARS2 expression predicted better PFS and OS; dual-low expression conferred the best prognosis (all P < 0.001). Multivariate Cox regression identified SARS2 expression and CRS as independent predictors of PFS, and SARS2 expression as an independent predictor of OS. These findings indicate that CRS represents an important post-NACT pathological prognostic marker, whereas pretreatment ACTN4 and SARS2 expression may help predict NACT response and survival outcomes in HGSOC. The combined assessment of ACTN4 and SARS2 may provide a potential pretreatment biomarker for evaluating chemotherapy response and prognosis.