Prognostic associations of PFAS in ovarian cancer: Insights from exploratory analysis

Ovarian cancer (OC), a deadliest gynecological malignancy, lacks reliable predictive biomarkers for its heterogeneous clinical outcomes. Per- and polyfluoroalkyl substances (PFAS) are persisting endocrine disruptors potentially affecting female reproductive health, but their roles in OC remain unclear. We aimed to investigate the possible associations between PFAS and OC prognosis.

PFAS-related mRNAs were acquired from the Comparative Toxicogenomics resource, mRNAs expression and clinicopathological information of OC were extracted from The Cancer Genome Atlas and Gene Expression Omnibus databases. Prognostic factors were selected using Cox proportional hazards regression (cox), random survival forest, and lasso regression methods. The prediction models for overall survival (OS) and progression free survival (PFS) were further constructed by cox regression. Molecular docking was performed to assess the binding capacity of PFAS to certain mRNAs. The effects of PFAS on the phenotype of OC cells were analyzed by quantitative real-time PCR, CCK8, migration, and invasion detection.

PFAS-derived risk scores were constructed based on prognosis-related mRNAs, which were independent predictors for prognosis of OC. PFAS-derived risk scores showed 1-year time-dependent AUC values 0.71/0.67/0.66 (OS) and 0.70/0.65/0.61 (PFS) in training/testing/external validation sets, respectively. Drug sensitivity analysis indicated that patients with lower risk score may derive greater benefit from chemotherapy drugs. Molecular docking analysis suggested a high affinity between PFAS and the targeted proteins of prognosis-related mRNAs. In vitro experiments further substantiated that perfluorooctanoic acid exposure promoted the malignant phenotypes of OC cells and the changes of SLC22A2, SPOCK3, and APOD expressions.

In this exploratory study, PFAS-derived risk scores showed potential for predicting OC prognosis and might offer insights relevant to clinical treatment strategies, pointing to the potential prognostic role of PFAS in OC.