SRS127 - Afadin (AFDN) and the nectin protein complex in the development of metastasis of breast cancers

Abstract Introduction AFDN (Afadin, also known as AF6 or MLLT4) is a cytoskeletal-associated protein originally identified in epithelial ovarian cancer cells. It serves as a key adaptor linking nectins to actin filaments, a connection potentially regulated by Ras signalling. Through homophilic and heterophilic interactions, nectins form adherens and tight junctions essential for cell adhesion. Despite their functional importance, the role of AFDN and its nectin partners in breast cancer remains poorly understood. This study assessed the prognostic significance of the AFDN–nectin complex in breast cancer progression and patient outcomes. Methods Transcript expression profiles of AFDN and nectins were analyzed in a Cardiff breast cancer cohort (n = 134) and correlated with disease stage and clinical outcome. Results AFDN expression showed significant co-expression with Nectin1 (P < 0.001) and Nectin3 (P = 0.004) in both breast tumours and normal mammary tissues (P < 0.001 for both). An integrated expression signature of AFDN and nectins demonstrated strong prognostic value (AUC = 0.223, P = 4.339 × 10⁻⁷) and predictive power for favourable overall survival (OS) (P = 0.00018, HR = 0.724, 95% c.i.: 0.599–0.875). The positive prognostic effect was most pronounced in HER4-positive, HER2-positive, and HER2(+)/ER(−) subtypes (all P < 0.0001). Importantly, the AFDN/nectin expression profile remained independently associated with OS after adjusting for clinical, pathological, and hormonal factors (HR = 0.434, 95% c.i.: 0.273–0.691, P = 0.00043). Conclusions To our knowledge, this is the first demonstration of a prognostic link between AFDN–nectin expression and breast cancer outcomes. Given the limited research on these proteins in breast cancer, the AFDN–nectin complex represents a promising target for further clinical investigation.